Stereotaxic Surgery as a Method to Deliver Epigenetic Editing Constructs in Rodent Brain.

Modern neuroscience research is increasingly discovering that alterations in epigenetic states within key brain cells is correlated with brain diseases. These epigenetic alterations may include changes in histone post-translational modifications and/or DNA modifications, all of which affect transcription and other gene expression programs within the brain cells that comprise central brain regions. However, the exact causal contribution of these epigenome changes to brain disease cannot be elucidated in the absence of direct in vivo manipulations in the implicated brain areas. Combining the design and creation of epigenetic editing constructs, gene delivery strategies, and stereotaxic surgery enables neuroscience researchers to target and manipulate the epigenetic state of the brain cells of laboratory rodents in a locus-specific manner and test its causal contribution to disease-related pathology and behaviors. Here, we describe the surgical protocol utilized by our group and others, which is optimized for herpes simplex virus delivery into the mouse brain, although the protocol outlined herein could be applied for delivery of adeno-associated viruses, lentiviruses, or nonviral gene-delivery methods in both mice and rats. The method allows for the overexpression of engineered DNA-binding proteins for direct and targeted epigenome editing in rodent brain with excellent spatiotemporal control. Nearly any brain region of interest can be targeted in rodents at every stage of postnatal life. Owing to the versatility, reproducibility, and utility of this technique, it is an important method for any laboratory interested in studying the cellular, circuit, and behavioral consequences of manipulating the brain epigenome in laboratory rodents.

Transient Ageusia and Dysgeusia Following Thalamic Cyst Drainage.

Taste consists of sensation and perception. Specific neural structures transmit a stimulus from the taste buds to the gustatory cortex to generate taste sensation. Any disruption of this pathway, whether it affects sensation or perception, can result in taste disorders. Stereotactic procedures involving the thalamus may result in gustatory complications. A 41-year-old female patient who underwent stereotactic drainage of a thalamic cyst suffered transient ageusia. Subsequently, she developed metallic taste perception. When her stereotactic plan was re-evaluated, it was noted that the posteromedial ventral thalamus nucleus was in the path of the needle tract and the needle had passed through it. Follow-up was recommended and her symptoms completely resolved within 2 months following surgery. Modern imaging techniques allow for the visualization of neural structures related to the sense of taste. Additionally, care must be taken when planning stereotactic procedures for such lesions.

Intentional Insertion of Air to Predict the Diagnostic Accuracy of Stereotactic Biopsy and a Uniform Grading System for Reporting.

BACKGROUND AND OBJECTIVES: Stereotactic biopsies are a relatively safe and reliable way of tissue diagnosis and characterization of eloquent area lesions/neoplasm. However, predicting the accuracy of the site of biopsy with the desired/planned site is not always possible. We describe a technique to identify the precise location of the biopsy site in the post-operative computed tomography (CT) scan using the injection of a low volume of air into the biopsy cannula. METHODS: Hundred consecutive biopsies were performed in 80 adults/20 children (59 males/41 females, median age 51 years) over 3 years, consisting of 75 frameless and 25 frame-based stereotactic biopsies. After the biopsy specimens had been collected, a small volume of air (median 1 cc) was injected into the site. Post-operative CT was done within 4 hours of the biopsy to see the site of the air bubble, and the same was correlated with the histopathological accuracy. RESULTS: Intra-cranial air in the selected target was present in 95 patients (Grade 1 and 2), while the air was seen in the track (Grade 3) in 3% and at an unrelated site (Grade 4) in 2% of cases. Both Grade 4 biopsies were negative on histopathology (diagnostic yield = 98%). Two negative biopsies were reported, which were both predicted with the Grade 4 biopsy. The grading allowed uniform reporting across series and eliminated the chance of upgrading/downgrading the report due to wrong site sampling within the lesion/neoplasm. CONCLUSION: The air-injection manoeuvre proposed for use in stereotactic biopsies of intra-cranial mass lesions is a safe and reliable technique that allows the exact biopsy site to be located without any related complications.

Comparison of Navigated and Frame-Based Stereotactic Biopsy-A Single-Center Cohort Study.

Background and Objectives: As brain lesions present complex diagnostic challenges, accurate tissue sampling via biopsy is critical for effective treatment planning. Traditional frame-based stereotactic biopsy has been complemented by navigated biopsy techniques, leveraging advancements in imaging and navigation technology. This study aims to compare the navigated and frame-based stereotactic biopsy methods in a clinical setting, evaluating their efficacy, safety, and diagnostic outcomes to determine the optimal approach for precise brain lesion targeting. Materials and Methods: retrospective analysis was conducted on patients who underwent brain biopsies between January 2017 and August 2023 at an academic medical center. Data on patient demographics, clinical characteristics, biopsy technique (navigated vs. frame-based), and outcomes including accuracy, complications, and hospital stay duration were analyzed. Results: The cohort comprised 112 patients, with no significant age or gender differences between groups. Symptoms leading to biopsy were predominantly diminished muscle strength (42.0%), cognitive issues (28.6%), and aphasia (24.1%). Tumors were most common in the deep hemisphere (24.1%). The median hospital stay was 5 days, with a rehospitalization rate of 27.7%. Complications occurred in 4.47% of patients, showing no significant difference between biopsy methods. However, navigated biopsies resulted in fewer samples (p < 0.001) but with comparable diagnostic accuracy as frame-based biopsies. Conclusions: Navigated and frame-based stereotactic biopsies are both effective and safe, with comparable accuracy and complication rates. The choice of technique should consider lesion specifics, surgeon preference, and technological availability. The findings highlight the importance of advanced neurosurgical techniques in enhancing patient care and outcomes.

Clinical application of CT-assisted body surface localization combined with intraoperative stereotactic anatomical localization in thoracoscopic lung nodule resection: a single-centre retrospective study.

BACKGROUND: Today, the detection rate of lung nodules is increasing. Some of these nodules may become malignant. Thus, timely resection of potentially malignant nodules is essential. However, Identifying the location of nonsurface or soft-textured nodules during surgery is challenging. Various localization techniques have been developed to accurately identify lung nodules. Common methods include preoperative CT-guided percutaneous placement of hook wires and microcoils. Nonetheless, these procedures may cause complications such as pneumothorax and haemothorax. Other methods regarding localization of pulmonary nodules have their own drawbacks. We conducted a clinical study which was retrospective to identify a safe, accurate and suitable method for determining lung nodule localization. To evaluate the clinical value of CT-assisted body surface localization combined with intraoperative stereotactic anatomical localization in thoracoscopic lung nodule resection. METHODS: We retrospectively collected the clinical data of 120 patients who underwent lung nodule localization and resection surgery at the Department of Thoracic Surgery, First Affiliated Hospital of Bengbu Medical College, from January 2020 to January 2022. Among them, 30 patients underwent CT-assisted body surface localization combined with intraoperative stereotactic anatomical localization, 30 patients underwent only CT-assisted body surface localization, 30 patients underwent only intraoperative stereotactic anatomical localization, and 30 patients underwent CT-guided percutaneous microcoil localization. The success rates, complication rates, and localization times of the four lung nodule localization methods were statistically analysed. RESULTS: The success rates of CT-assisted body surface localization combined with intraoperative stereotactic anatomical localization and CT-guided percutaneous microcoil localization were both 96.7%, which were significantly higher than the 70.0% success rate in the CT-assisted body surface localization group (P < 0.05). The complication rate in the combined group was 0%, which was significantly lower than the 60% in the microcoil localization group (P < 0.05). The localization time for the combined group was 17.73 ± 2.52 min, which was significantly less than that (27.27 ± 7.61 min) for the microcoil localization group (P < 0.05). CONCLUSIONS: CT-assisted body surface localization combined with intraoperative stereotactic anatomical localization is a safe, painless, accurate, and reliable method for lung nodule localization.

Protocol for fiber photometry recording from deep brain regions in head-fixed mice.

To exclude the influence of motion on in vivo calcium imaging, animals usually need to be fixed. However, the whole-body restraint can cause stress in animals, affecting experimental results. In addition, some brain regions are prone to bleeding during surgery, which lowers the success rate of calcium imaging. Here, we present a protocol for calcium imaging using heparin-treated fiber in head-fixed mice. We describe steps for stereotaxic surgery, including virus injection and optic fiber implantation, fiber photometry, and data analysis. For complete details on the use and execution of this protocol, please refer to Du et al.1.

Speech decoding from stereo-electroencephalography (sEEG) signals using advanced deep learning methods.

Objective.Brain-computer interfaces (BCIs) are technologies that bypass damaged or disrupted neural pathways and directly decode brain signals to perform intended actions. BCIs for speech have the potential to restore communication by decoding the intended speech directly. Many studies have demonstrated promising results using invasive micro-electrode arrays and electrocorticography. However, the use of stereo-electroencephalography (sEEG) for speech decoding has not been fully recognized.Approach.In this research, recently released sEEG data were used to decode Dutch words spoken by epileptic participants. We decoded speech waveforms from sEEG data using advanced deep-learning methods. Three methods were implemented: a linear regression method, an recurrent neural network (RNN)-based sequence-to-sequence model (RNN), and a transformer model.Main results.Our RNN and transformer models outperformed the linear regression significantly, while no significant difference was found between the two deep-learning methods. Further investigation on individual electrodes showed that the same decoding result can be obtained using only a few of the electrodes.Significance.This study demonstrated that decoding speech from sEEG signals is possible, and the location of the electrodes is critical to the decoding performance.

Diagnostics and treatment delay in primary central nervous system lymphoma: What the neurosurgeon should know.

PURPOSE: The gold standard for diagnostics in primary central nervous system lymphoma (PCNSL) is histopathological diagnosis after stereotactic biopsy. Yet, PCNSL has a multidisciplinary diagnostic work up, which associated with diagnostic delay and could result in treatment delay. This article offers recommendations to neurosurgeons involved in clinical decision-making regarding (novel) diagnostics and care for patients with PCNSL with the aim to improve uniformity and timeliness of the diagnostic process for patients with PCNSL. METHODS: We present a mini review to discuss the role of stereotactic biopsy in the context of novel developments in diagnostics for PCNSL, as well as the role for cytoreductive surgery. RESULTS: Cerebrospinal fluid-based diagnostics are supplementary and cannot replace stereotactic biopsy-based diagnostics. CONCLUSION: Histopathological diagnosis after stereotactic biopsy of the brain remains the gold standard for diagnosis. Additional diagnostics should not be a cause of diagnostic delay. There is currently no sufficient evidence supporting cytoreductive surgery in PCNSL, with recent studies showing contradictive data and suboptimal study designs.

The United States Stereotactic EEG Survey: Current Practice and Future Opportunities.

PURPOSE: Stereotactic EEG (SEEG) is being increasingly used in the intracranial evaluation of refractory epilepsy in the United States. A 2022 survey of SEEG practices among National Association of Epilepsy Centers tertiary referral (NAEC level IV) centers found largely similar practices across institutions. However, a few significant differences were noted in technical and patient care practice, and in the level of SEEG background training. In the year since publication, we review the identified challenges facing SEEG practice and suggest specific corrective action. CONCLUSIONS: Stereotactic EEG has rapidly become the principal method for intracranial EEG monitoring in epilepsy surgery centers in the United States. The rate of adoption of SEEG is currently higher than the growth of invasive monitoring overall. Most report similar indications for SEEG, although significant variability exists in personnel expertise and technical and patient care practice. Consensus statements, guidelines, and review of postgraduate training curricula are urgently needed to benchmark SEEG practice and develop appropriate skillsets in the next generation of practitioners in the United States.

The Voyage of SEEG.

SUMMARY: It took 50 years for stereoelectroencephalography (SEEG) to cross the Atlantic. Conceived and designed before the advent of computers and modern technology, this method turned out to be perfectly suited to brain imaging and modern video and electrophysiological tools. It eventually benefited from robotics and signal processing. However, a critical step remains accurate electrode implantation, which is based on individual patients' noninvasive phase I data. A limiting factor, especially in MRI-negative cases, is a thorough perictal and postictal clinical testing for ensuring meaningful electroclinical correlations. Adapted epilepsy monitoring units' architecture and specific technicians and nurses training are required to improve the granularity of information needed to generate valid hypotheses on localization. SEEG interpretation is based on a knowledge base in neural networks, cognitive/behavioral neuroscience, and electrophysiology quite distinct from electroencephalography. Tailored to the needs of focal epilepsy complexity exploration, SEEG does not fit well with simplification. Specific teaching and development of clinical research inside the epilepsy monitoring units will help to flatten the team learning curve and to build knowledge base from shared clinical experience.

Back to Basics: Care of the Stereotactic EEG Implanted Patient.

PURPOSE: Stereotactic EEG (SEEG) is gaining increasing popularity in the United States. Patients undergoing SEEG have unique challenges, and their needs are different compared with noninvasive cases. We aim to describe the medical, nursing, and other institutional practices of SEEG evaluations among tertiary referral (level IV) epilepsy centers accredited by the National Association of Epilepsy Centers. METHODS: We analyzed data obtained from a Research Electronic Data Capture (REDCap) survey we formulated and distributed to directors of all level IV epilepsy centers listed by the National Association of Epilepsy Center. Most questions were addressed to the adult and pediatric SEEG programs separately. RESULTS: Among 199 epilepsy center directors invited to complete the survey, 90 (45%) responded. Eighty-three centers (92%) reported they perform SEEG evaluations. Of the 83 respondents, 56 perform SEEG in adult and 47 in pediatric patients. Twenty-two centers evaluate both pediatric and adult subjects. The highest concordance of SEEG workflow was in (1) epilepsy monitoring unit stay duration (1-2 weeks, 79% adult and 85% pediatric programs), (2) use of sleep deprivation (94% both adult and pediatric) and photic stimulation (79% adult and 70% pediatric) for seizure activation, (3) performing electrical cortical stimulation at the end of SEEG evaluation after spontaneous seizures are captured (84% adult and 88% pediatric), and (4) daily head-wrap inspection (76% adult and 80% pediatric). Significant intercenter variabilities were noted in the other aspects of SEEG workflow. CONCLUSIONS: Results showed significant variability in SEEG workflow across polled centers. Prospective, multicenter protocols will help the future development and harmonization of optimal practice patterns.

Stereoelectroencephalography of the Deep Brain: Basal Ganglia and Thalami.

SUMMARY: Stereoelectroencephalography (SEEG) has emerged as a transformative tool in epilepsy surgery, shedding light on the complex network dynamics involved in focal epilepsy. This review explores the role of SEEG in elucidating the role of deep brain structures, namely the basal ganglia and thalamus, in epilepsy. SEEG advances understanding of their contribution to seizure generation, propagation, and control by permitting precise and minimally invasive sampling of these brain regions. The basal ganglia, comprising the subthalamic nucleus, globus pallidus, substantia nigra, and striatum, have gained recognition for their involvement in both focal and generalized epilepsy. Electrophysiological recordings reveal hyperexcitability and increased synchrony within these structures, reinforcing their role as critical nodes within the epileptic network. Furthermore, low-frequency and high-frequency stimulation of the basal ganglia have demonstrated potential in modulating epileptogenic networks. Concurrently, the thalamus, a key relay center, has garnered prominence in epilepsy research. Disrupted thalamocortical connectivity in focal epilepsy underscores its significance in seizure maintenance. The thalamic subnuclei, including the anterior nucleus, centromedian, and medial pulvinar, present promising neuromodulatory targets, suggesting pathways for personalized epilepsy therapies. The prospect of multithalamic SEEG and thalamic SEEG stimulation trials has the potential to revolutionize epilepsy management, offering tailored solutions for challenging cases. SEEG's ability to unveil the dynamics of deep brain structures in epilepsy promises enhanced and personalized epilepsy care in our new era of precision medicine. Until deep brain SEEG is accepted as a standard of care, a rigorous informed consent process remains paramount for patients for whom such an exploration is proposed.

In Search of a Common Language: The Standardized Electrode Nomenclature for Stereoelectroencephalography Applications.

PURPOSE: Stereoelectroencephalography (SEEG) is widely performed on individuals with medically refractory epilepsy for whom invasive seizure localization is desired. Despite increasing adoption in many centers across the world, no standardized electrode naming convention exists, generating confusion among both clinical and research teams. METHODS: We have developed a novel nomenclature, named the Standardized Electrode Nomenclature for SEEG Applications system. Concise, unique, informative, and unambiguous labels provide information about entry point, deep targets, and relationships between electrodes. Inter-rater agreement was evaluated by comparing original electrode names from 10 randomly sampled cases (including 136 electrodes) with those prospectively assigned by four additional blinded raters. RESULTS: The Standardized Electrode Nomenclature for SEEG Application system was prospectively implemented in 40 consecutive patients undergoing SEEG monitoring at our institution, creating unique electrode names in all cases, and facilitating implantation design, SEEG recording and mapping interpretation, and treatment planning among neurosurgeons, neurologists, and neurophysiologists. The inter-rater percent agreement for electrode names among two neurosurgeons, two epilepsy neurologists, and one neurosurgical fellow was 97.5%. CONCLUSIONS: This standardized naming convention, Standardized Electrode Nomenclature for SEEG Application, provides a simple, concise, reproducible, and informative method for specifying the target(s) and relative position of each SEEG electrode in each patient, allowing for successful sharing of information in both the clinical and research settings. General adoption of this nomenclature could pave the way for improved communication and collaboration between institutions.

Clinical Utility of Sleep Recordings During Presurgical Epilepsy Evaluation With Stereo-Electroencephalography: A Systematic Review.

SUMMARY: Although the role of sleep in modulating epileptic activity is well established, many epileptologists overlook the significance of considering sleep during presurgical epilepsy evaluations in cases of drug-resistant epilepsy. Here, we conducted a comprehensive literature review from January 2000 to May 2023 using the PubMed electronic database and compiled evidence to highlight the need to revise the current clinical approach. All articles were assessed for eligibility by two independent reviewers. Our aim was to shed light on the clinical value of incorporating sleep monitoring into presurgical evaluations with stereo-electroencephalography. We present the latest developments on the important bidirectional interactions between sleep and various forms of epileptic activity observed in stereo-electroencephalography recordings. Specifically, epileptic activity is modulated by different sleep stages, peaking in non-rapid eye movement sleep, while being suppressed in rapid eye movement sleep. However, this modulation can vary across different brain regions, underlining the need to account for sleep to accurately pinpoint the epileptogenic zone during presurgical assessments. Finally, we offer practical solutions, such as automated sleep scoring algorithms using stereo-electroencephalography data alone, to seamlessly integrate sleep monitoring into routine clinical practice. It is hoped that this review will provide clinicians with a readily accessible roadmap to the latest evidence concerning the clinical utility of sleep monitoring in the context of stereo-electroencephalography and aid the development of therapeutic and diagnostic strategies to improve patient surgical outcomes.

Escaping the Procrustean Bed: A Perspective on Pediatric Stereoelectroencephalography.

SUMMARY: Stereoelectroencephalography is an established, hypothesis-driven method for investigating refractory epilepsy. There are special considerations and some limitations that apply to children who undergo stereoelectroencephalography. A key principle in stereoelectroencephalography is taking an individualized approach to investigating refractory epilepsy. A crucial factor for success in a personalized pediatric epilepsy surgery is understanding some of the fundamental and unique aspects of it, including, but not limited to, diverse etiology, epilepsy syndromes, maturation, and age-related characteristics as well as neural plasticity. Such features are reflected in the ontogeny of semiology and electrophysiology. In addition, special considerations are taken into account during cortical stimulation in children. Stereoelectroencephalography can guide a tailored surgical intervention where it is sufficient to render the patient seizure-free but it also lessens collateral damage with a minimum or no functional deficit. Epilepsy surgery outcomes remain stagnant despite advances in noninvasive testing modalities. A stereoelectroencephalography "way of thinking" and guided mentorship may influence outcomes positively.

The changing landscape of electrical stimulation language mapping with subdural electrodes and stereoelectroencephalography for pediatric epilepsy: A literature review and commentary.

Electrical stimulation mapping (ESM) is used to locate the brain areas supporting language directly within the human cortex to minimize the risk of functional decline following epilepsy surgery. ESM is completed by utilizing subdural grid or depth electrodes (stereo-electroencephalography [sEEG]) in combination with behavioral evaluation of language. Despite technological advances, there is no standardized method of assessing language during pediatric ESM. To identify current clinical practices for pediatric ESM of language, we surveyed neuropsychologists in the Pediatric Epilepsy Research Consortium. Results indicated that sEEG is used for functional mapping at >80% of participating epilepsy surgery centers (n = 13/16) in the United States. However, >65% of sites did not report a standardized protocol to map language. Survey results indicated a clear need for practice recommendations regarding ESM of language. We then utilized PubMed/Medline and PsychInfo to identify 42 articles that reported on ESM of language, of which 18 met inclusion criteria, which included use of ESM/signal recording to localize language regions in children (<21 years) and a detailed account of the procedure and language measures used, and region-specific language localization outcomes. Articles were grouped based on the language domain assessed, language measures used, and the brain regions involved. Our review revealed the need for evidence-based clinical guidelines for pediatric language paradigms during ESM and a standardized language mapping protocol as well as standardized reporting of brain regions in research. Relevant limitations and future directions are discussed with a focus on considerations for pediatric language mapping.

Depth versus surface: A critical review of subdural and depth electrodes in intracranial electroencephalographic studies.

Intracranial electroencephalographic (IEEG) recording, using subdural electrodes (SDEs) and stereoelectroencephalography (SEEG), plays a pivotal role in localizing the epileptogenic zone (EZ). SDEs, employed for superficial cortical seizure foci localization, provide information on two-dimensional seizure onset and propagation. In contrast, SEEG, with its three-dimensional sampling, allows exploration of deep brain structures, sulcal folds, and bihemispheric networks. SEEG offers the advantages of fewer complications, better tolerability, and coverage of sulci. Although both modalities allow electrical stimulation, SDE mapping can tessellate cortical gyri, providing the opportunity for a tailored resection. With SEEG, both superficial gyri and deep sulci can be stimulated, and there is a lower risk of afterdischarges and stimulation-induced seizures. Most systematic reviews and meta-analyses have addressed the comparative effectiveness of SDEs and SEEG in localizing the EZ and achieving seizure freedom, although discrepancies persist in the literature. The combination of SDEs and SEEG could potentially overcome the limitations inherent to each technique individually, better delineating seizure foci. This review describes the strengths and limitations of SDE and SEEG recordings, highlighting their unique indications in seizure localization, as evidenced by recent publications. Addressing controversies in the perceived usefulness of the two techniques offers insights that can aid in selecting the most suitable IEEG in clinical practice.