Laser interstitial thermal therapy for new and recurrent meningioma: a prospective and retrospective case series.

OBJECTIVE: Meningiomas are the most common primary brain tumors in adults and a subset are aggressive lesions resistant to standard therapies. Laser interstitial thermal therapy (LITT) has been successfully applied to other brain tumors, and recent work aims to explore the safety and long-term outcome experiences of LITT for both new and recurrent meningiomas. The authors' objective was to report safety and outcomes data of the largest cohort of LITT-treated meningioma patients to date. METHODS: Eight United States-based hospitals enrolled patients with meningioma in the Laser Ablation of Abnormal Neurological Tissue Using Robotic NeuroBlate System (LAANTERN) prospective multicenter registry and/or contributed additional retrospective enrollments for this cohort study. Demographic, procedural, safety, and outcomes data were collected and analyzed using standard statistical methods. RESULTS: Twenty adult patients (12 prospective and 8 retrospective) with LITT-targeted meningiomas were accrued. Patients underwent LITT for new (6 patients) and recurrent (14 patients) tumors (ranging from the 1st to 12th recurrence). The 30-day complication rate was 10%. Twenty percent of patients (4/20) had exhausted all other treatment options. Median length of follow-up was 1.3 years. One-third of new (2/6) and one-half of recurrent (7/14) meningiomas had disease progression during follow-up. One-year estimated local control (LC), progression-free survival, and overall survival rates were 55.3%, 48.4%, and 86.3%, respectively. In the 12 patients who had ≥ 91% ablative coverage, 1-year estimated LC was 61.4%. The complication rate was 10% (2/20), with 1 complication being transient and resolving postoperatively. CONCLUSIONS: This cohort study supports the safety of the procedure for this tumor type. LITT can offer a much-needed treatment option, especially for patients with multiply recurrent meningiomas who have limited remaining alternatives.

Stereo-electroencephalographic seizure localization in patients with mesial temporal sclerosis: A single center experience.

Objective: Epilepsy patients with mesial temporal sclerosis (MTS) on imaging who are drug-resistant usually undergo epilepsy surgery without previous invasive evaluation. However, up to one-third of patients are not seizure-free after surgery. Prior studies have identified risk factors for surgical failure, but it is unclear if they are associated with bilateral or discordant seizure onset. Methods: In this retrospective case series, we identified 17 epilepsy patients who had MRI-confirmed MTS but received invasive stereo-EEG (SEEG) evaluation before definitive intervention. We analyzed their presurgical risk factors in relation to SEEG seizure onset localization and MRI/SEEG concordance. Results: SEEG ictal onset was concordant with MTS localization (i.e. seizures started only from the hippocampus with MTS) in 5 out of 13 patients with unilateral MTS (UMTS) and in 3 out of 4 patients with bilateral MTS.No statistically significant association regarding concordance of SEEG ictal onset and MTS location was found in patients with such risk factors as a history of non-mesial temporal aura, frequent focal to bilateral tonic-clonic seizures, prior viral brain infection, or family history of epilepsy. Nine out of 13 UMTS patients had resective surgery only, 5 out of 9 (56 %) have Engel class I outcome at most recent follow-up (median 46.5 months, range 22-91 months). In Engel class I cohort, the SEEG ictal onset was concordant with MTS location in 3 out of 5 patients, and 2 patients had ipsilateral temporal neocortical ictal onset. Conclusions: Our findings suggest that patients with MTS might have discordant SEEG ictal onset (in 61.5% patients with UMTS in presented cohort), which may explain poor surgical outcome after destructive surgery in these cases. Significance: Although no statistically significant association was found in this under-powered study, these findings could be potentially valuable for future meta-analyses.

Bibliometric Analysis and Applications of a Modified H-Index Examining the Research Productivity of Neurosurgery Faculty at High-Ranking Academic Institutions.

OBJECTIVE: A major critique of the h-index is that it may be inflated by noncritical authorship. We propose a modified h-index (hm), incorporating critical authorship, complementary to the h-index. We analyze its relationship to the traditional h-index, and how each varies across professional categories relevant to academic neurosurgery. This analysis is not meant to critique authorship decisions, affect career development, alter academic legacy, or imply that the concepts of team science or midlevel authorship contributions are not valuable. METHODS: H-indices and hms were gathered and computed for clinical neurosurgical faculty at the top 32 ranked academic neurosurgical programs based on the current literature. Hm was computed for faculty at each program, using articles in which the individual was first, second, last, or co-corresponding author. Individuals were further identified based on chair status, leadership status, neurosurgical subspecialty, and National Institutes of Health funding status. Further analysis was performed to determine factors influencing h-index and hm. RESULTS: The median h-index for the 225 physicians included in the final dataset is 48 (interquartile range [IQR], 39-61), whereas the median hm was 32 (IQR, 24-43). The median difference between h-index and hm is 15 (IQR, 10-23). The median hm/h was 64% (IQR, 57-74). National Institutes of Health funding and subspecialty (neurosurgical oncology, neurocritical care, and cerebrovascular) were associated with significant change from h to hm. CONCLUSIONS: The h-index can be influenced by noncritical authorship, and hm, using critical contributions, can be used as a complement reflecting critical academic output in neurosurgery. Leaders deciding on hiring or promotion should consider disparities in productivity predicated on noncritical authorship contributions.

Seizure onset patterns predict outcome after stereo-electroencephalography-guided laser amygdalohippocampotomy.

OBJECTIVE: Stereotactic laser amygdalohippocampotomy (SLAH) is an appealing option for patients with temporal lobe epilepsy, who often require intracranial monitoring to confirm mesial temporal seizure onset. However, given limited spatial sampling, it is possible that stereotactic electroencephalography (stereo-EEG) may miss seizure onset elsewhere. We hypothesized that stereo-EEG seizure onset patterns (SOPs) may differentiate between primary onset and secondary spread and predict postoperative seizure control. In this study, we characterized the 2-year outcomes of patients who underwent single-fiber SLAH after stereo-EEG and evaluated whether stereo-EEG SOPs predict postoperative seizure freedom. METHODS: This retrospective five-center study included patients with or without mesial temporal sclerosis (MTS) who underwent stereo-EEG followed by single-fiber SLAH between August 2014 and January 2022. Patients with causative hippocampal lesions apart from MTS or for whom the SLAH was considered palliative were excluded. An SOP catalogue was developed based on literature review. The dominant pattern for each patient was used for survival analysis. The primary outcome was 2-year Engel I classification or recurrent seizures before then, stratified by SOP category. RESULTS: Fifty-eight patients were included, with a mean follow-up duration of 39 ± 12 months after SLAH. Overall 1-, 2-, and 3-year Engel I seizure freedom probability was 54%, 36%, and 33%, respectively. Patients with SOPs, including low-voltage fast activity or low-frequency repetitive spiking, had a 46% 2-year seizure freedom probability, compared to 0% for patients with alpha or theta frequency repetitive spiking or theta or delta frequency rhythmic slowing (log-rank test, p = .00015). SIGNIFICANCE: Patients who underwent SLAH after stereo-EEG had a low probability of seizure freedom at 2 years, but SOPs successfully predicted seizure recurrence in a subset of patients. This study provides proof of concept that SOPs distinguish between hippocampal seizure onset and spread and supports using SOPs to improve selection of SLAH candidates.

Stereo-EEG Evaluation and Surgical Treatment in Patients With Drug-Resistant Focal Epilepsy Associated With Nodular Heterotopia.

PURPOSE: Nodular heterotopia (NH) is a common cause of drug-resistant epilepsy. Only limited studies detail the treatment of NH with laser interstitial thermal therapy and none analyze the relation between epileptogenicity and NH location. METHODS: We retrospectively studied nine patients with drug-resistant epilepsy and NH who underwent stereoelectroencephalography and subsequent epilepsy surgery. Nodular heterotopia in the frontal lobes or along the bodies of the lateral ventricles was classified as anterior NH. Nodular heterotopia in the trigones, temporal or occipital horns, or temporal lobes was classified as posterior NH. Nodular heterotopia in both anterior and posterior locations was classified as diffuse NH. Interictal and ictal stereoelectroencephalography were analyzed, and patients were followed postoperatively to assess outcomes. RESULTS: Of the six patients who underwent nine laser interstitial thermal therapy procedures either in isolation or in combination with other surgical therapies, four patients were Engel Ia, one was Engel IIb, and one was Engel IIIa, with an average follow-up of 22.8 months. All patients with posterior NH had interictal epileptiform abnormalities and seizures originating from the posterior NH. None of the patients with anterior NH had epileptiform activity recorded from their NH. CONCLUSION: Laser interstitial thermal therapy alone or in combination with other surgical therapies is an effective treatment in those with drug-resistant epilepsy because of NH, even in those with extensive NH and broad seizure onset. We observed a trend suggesting that posterior NH are more likely to be epileptogenic compared with anterior NH and recommend that in patients with anterior NH, alternative epilepsy etiologies and stereoelectroencephalography implantation strategies be considered.

Vagus nerve stimulation paired with rehabilitation for stroke: Implantation experience from the VNS-REHAB trial.

OBJECTIVE: Vagus Nerve Stimulation (VNS) paired with rehabilitation delivered by the Vivistim® Paired VNS™ System was approved by the FDA in 2021 to improve motor deficits in chronic ischemic stroke survivors with moderate to severe arm and hand impairment. Vagus nerve stimulators have previously been implanted in over 125,000 patients for treatment-resistant epilepsy and the surgical procedure is generally well-tolerated and safe. In this report, we describe the Vivistim implantation procedure, perioperative management, and complications for chronic stroke survivors enrolled in the pivotal trial. METHODS: The pivotal, multisite, randomized, triple-blind, sham-controlled trial (VNS-REHAB) enrolled 108 participants. All participants were implanted with the VNS device in an outpatient procedure. Thrombolytic agents were temporarily discontinued during the perioperative period. Participants were discharged within 48 hrs and started rehabilitation therapy approximately 10 days after the Procedure. RESULTS: The rate of surgery-related adverse events was lower than previously reported for VNS implantation for epilepsy and depression. One participant had vocal cord paresis that eventually resolved. There were no serious adverse events related to device stimulation. Over 90% of participants were taking antiplatelet drugs (APD) or anticoagulants and no adverse events or serious adverse events were reported as a result of withholding these medications during the perioperative period. CONCLUSIONS: This study is the largest, randomized, controlled trial in which a VNS device was implanted in chronic stroke survivors. Results support the use of the Vivistim System in chronic stroke survivors, with a safety profile similar to VNS implantations for epilepsy and depression.

Non-lesional mesial temporal lobe epilepsy requires bilateral invasive evaluation.

PURPOSE: Mesial temporal lobe epilepsy (MTLE) usually responds well to surgical treatment, although in non-lesional cases up to 50% of patients experience seizure relapse. The possibility of bilateral independent seizure onset should be considered as a reason for epilepsy surgery failure. METHODS: In a cohort of 177 patients who underwent invasive presurgical evaluation with stereo-tactically placed electrodes in two level four epilepsy centers, 29 had non-lesional MTLE. Invasive evaluation results are described. RESULTS: Among 29 patients with non-lesional MRI and mesial temporal lobe seizure onset recorded during stereo-EEG (SEEG) evaluation, four patients with unilateral preimplantation hypothesis had independent bilateral mesial temporal seizures on SEEG despite of unilateral non-invasive evaluation data. Three of these patients were treated with bitemporal responsive neurostimulator system (RNS). Independent bilateral mesial temporal seizures have been confirmed on RNS ECoG (electrocorticography). The fourth patient underwent right anterior temporal lobectomy. CONCLUSION: We propose that patients with non-lesional mesial temporal lobe epilepsy would benefit from bilateral invasive evaluation of mesial temporal structures to predict those patients who would be at most risk for surgical failure. Neurostimulaiton could be an initial treatment option for patients with independent bitemporal seizure onset.

Longitudinal Differences in Human Hippocampal Connectivity During Episodic Memory Processing.

The question of longitudinal hippocampal functional specialization is critical to human episodic memory because an accurate understanding of this phenomenon would impact theories of mnemonic function and entail practical consequences for the clinical management of patients undergoing temporal lobe surgery. The implementation of the robotically assisted stereo electroencephalography technique for seizure mapping has provided our group with the opportunity to obtain recordings simultaneously from the anterior and posterior human hippocampus, allowing us to create an unparalleled data set of human subjects with simultaneous anterior and posterior hippocampal recordings along with several cortical regions. Using these data, we address several key questions governing functional hippocampal connectivity in human memory. First, we ask whether functional networks during episodic memory encoding and retrieval are significantly different for the anterior versus posterior hippocampus (PH). We also examine how connections differ across the 2-5 Hz versus 4-9 Hz theta frequency ranges, directly addressing the relative contribution of each of these separate bands in hippocampal-cortical interactions. While we report some overlapping connections, we observe evidence of distinct anterior versus posterior hippocampal networks during memory encoding related to frontal and parietal connectivity as well as hemispheric differences in aggregate connectivity. We frame these findings in light of the proposed AT/PM memory systems. We also observe distinct encoding versus retrieval connectivity patterns between anterior and posterior hippocampal networks, we find that overall connectivity is greater for the PH in the right hemisphere, and further that these networks significantly differ in terms of frontal and parietal connectivity. We place these findings in the context of existing theoretical treatments of human memory systems, especially the proposed AT/PM system. During memory retrieval, we observe significant differences between slow-theta (2-5 Hz) and fast-theta (4-9 Hz) connectivity between the cortex and hippocampus. Finally, we test how these distinct theta frequency oscillations propagate within the hippocampus, using phase slope index to estimate the direction slow-theta and fast-theta oscillations travel during encoding and retrieval. We uncover evidence that 2-5 Hz oscillations travel in the posterior-to-anterior direction, while 5-9 Hz oscillations travel from anterior-to-posterior. Taken together, our findings describe mnemonically relevant functional connectivity differences along the longitudinal axis of the human hippocampus that will inform interpretation of models of hippocampal function that seek to integrate rodent and human data.

Connectivity of the human insula: A cortico-cortical evoked potential (CCEP) study.

OBJECTIVE: The human insula is increasingly being implicated as a multimodal functional network hub involved in a large variety of complex functions. Due to its inconspicuous location and highly vascular anatomy, it has historically been difficult to study. Cortico-cortical evoked potentials (CCEPs), utilize low frequency stimulation to map cerebral networks. They were used to study connections of the human insula. METHODS: CCEP data was acquired from each sub-region of the dominant and non-dominant insula in 30 patients who underwent stereo-EEG. Connectivity strength to the various cortical regions was obtained via a measure of root mean square (RMS), calculated from each gyrus of the insula and ranked into weighted means. RESULTS: The results of all cumulative CCEP responses for each individual gyrus were represented by circro plots. Forty-nine individual CCEP pairs were stimulated across all the gyri from the right and left insula. In brief, the left insula contributed more greatly to language areas. Sensory function, pain, saliency processing and vestibular function were more heavily implicated from the right insula. Connections to the primary auditory cortex arose from both insula regions. Both posterior insula regions showed significant contralateral connectivity. Ipsilateral mesial temporal connections were seen from both insula regions. In visual function, we further report the novel finding of a direct connection between the right posterior insula and left visual cortex. SIGNIFICANCE: The insula is a major multi-modal network hub with the cerebral cortex having major roles in language, sensation, auditory, visual, limbic and vestibular functions as well as saliency processing. In temporal lobe epilepsy surgery failure, the insula may be implicated as an extra temporal cause, due to the strong mesial temporal connectivity findings.

Seizures in glioma patients: An overview of incidence, etiology, and therapies.

Gliomas are fatal brain tumors, and even low-grade gliomas (LGGs) have an average survival of less than a decade. Seizures are a common presentation of gliomas, particularly LGGs, and substantially impact quality of life. Glioma-related seizures differ from other focal epilepsies in their pathogenesis and in the likelihood of refractory epilepsy. We review factors that predict seizure activity and response to treatment, optimal pharmacologic and surgical management of glioma-related epilepsy, and the benefit of using newer anti-seizure medications in patients with gliomas. As surgery is so often beneficial with seizure reduction, we discuss oncologic and epilepsy surgery perspectives. Treatment of gliomas has the potential to ameliorate seizures and increase rates of seizure freedom. Prospective, well-powered studies are needed to provide more definitive answers for practitioners taking care of glioma patients with seizures.

Gamma oscillations during episodic memory processing provide evidence for functional specialization in the longitudinal axis of the human hippocampus.

The question of whether the anterior and posterior hippocampus serve different or complementary functional roles during episodic memory processing has been motivated by noteworthy findings in rodent experiments and from noninvasive studies in humans. Researchers have synthesized these data to postulate several models of functional specialization, However, the issue has not been explored in detail using direct brain recordings. We recently published evidence that theta power increases during episodic memory encoding occur in the posterior hippocampus in humans. In our current investigation we analyzed an expanded data set of 32 epilepsy patients undergoing stereo EEG seizure mapping surgery with electrodes precisely targeted to the anterior and posterior hippocampus simultaneously who performed an episodic memory task. Using a repeated measures design, we looked for an interaction between encoding versus retrieval differences in gamma oscillatory power and anterior versus posterior hippocampal location. Our findings are consistent with a recently articulated model (the HERNET model) favoring posterior hippocampal activation during retrieval related processing. We also tested for encoding versus retrieval differences in the preferred gamma frequency band (high versus low gamma oscillations) motivated by published rodent data.

Methylation of hypoxia-inducible factor (HIF)-1α by G9a/GLP inhibits HIF-1 transcriptional activity and cell migration.

Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator in response to hypoxia and its transcriptional activity is crucial for cancer cell mobility. Here we present evidence for a novel epigenetic mechanism that regulates HIF-1 transcriptional activity and HIF-1-dependent migration of glioblastoma cells. The lysine methyltransferases G9a and GLP directly bound to the α subunit of HIF-1 (HIF-1α) and catalyzed mono- and di-methylation of HIF-1α at lysine (K) 674 in vitro and in vivo. K674 methylation suppressed HIF-1 transcriptional activity and expression of its downstream target genes PTGS1, NDNF, SLC6A3, and Linc01132 in human glioblastoma U251MG cells. Inhibition of HIF-1 by K674 methylation is due to reduced HIF-1α transactivation domain function but not increased HIF-1α protein degradation or impaired binding of HIF-1 to hypoxia response elements. K674 methylation significantly decreased HIF-1-dependent migration of U251MG cells under hypoxia. Importantly, we found that G9a was downregulated by hypoxia in glioblastoma, which was inversely correlated with PTGS1 expression and survival of patients with glioblastoma. Therefore, our findings uncover a hypoxia-induced negative feedback mechanism that maintains high activity of HIF-1 and cell mobility in human glioblastoma.

Automatic Identification of Successful Memory Encoding in Stereo EEG of Refractory, Mesial Temporal Lobe Epilepsy.

Surgical resection of portions of the temporal lobe is the standard of care for patients with refractory mesial temporal lobe epilepsy. While this reduces seizures, it often results in an inability to form new memories, which leads to difficulties in social situations, learning, and suboptimal quality of life. Learning about the success or failure to form new memory in such patients is critical if we are to generate neuromodulation-based therapies. To this end, we tackle the many challenges in analyzing memory formation when their brains are recorded using stereoencephalography (sEEG) in a Free Recall task. Our contributions are threefold. First, we compute a rich measure of brain connectivity by computing the phase locking value statistic (synchrony) between pairs of regions, over hundreds of word memorization trials. Second, we leverage the rich information (over 400 values per pair of probed brain regions) to form consistent length feature vectors for classifier training. Third, we train and evaluate seven different types of classifier models and identify which ones achieve the highest accuracy and which brain features are most important for high accuracy. We assess our approach on data from 37 patients pre-resection surgery. We achieve up to 73% accuracy distinguishing successful from unsuccessful memory formation in the human brain from just 1.6 sec epochs of sEEG data.

Stereo-Encephalography Versus Subdural Electrodes for Seizure Localization.

In today's practice, epileptologists and neurosurgeons have several options for seizure localization with intracranial electrodes during phase II evaluations. Traditionally, centers in North America have used subdural electrode grids (SDE or SDG) for intracranial seizure localization. However, improvements in technology led to the popularization of stereo-encephalography (SEEG) using depth electrodes. Epilepsy surgery centers highest in volume now offer both SDE and SEEG for seizure localization. This article provides a general guide for considering SEEG versus SDE for intracranial seizure localization based on our experience with both. Several paradigmatic cases are used illustrate the advantages and disadvantages of the different approaches.

Cortico-cortical evoked potentials for sites of early versus late seizure spread in stereoelectroencephalography.

Cortico-cortical evoked potentials offer the possibility of understanding connectivity within seizure networks to improve diagnosis and more accurately identify candidates for seizure surgery. We sought to determine if cortico-cortical evoked potentials and post-stimulation oscillatory changes differ for sites of EARLY versus LATE ictal spread. 37 patients undergoing stereoelectroencephalography were tested using a cortico-cortical evoked potential paradigm. All electrodes were classified according to the speed of ictal spread. EARLY spread sites were matched to a LATE spread site equidistant from the onset zone. Root-mean-square was used to quantify evoked responses and post-stimulation gamma band power and coherence were extracted and compared. Sites of EARLY spread exhibited significantly greater evoked responses after stimulation across all patients (t(36)=2.973, p=0.004). Stimulation elicited enhanced gamma band activity at EARLY spread sites (t(36)=2.61, p=0.03, FDR corrected); this gamma band oscillation was highly coherent with the onset zone. Cortico-cortical evoked potentials and post-stimulation changes in gamma band activity differ between sites of EARLY versus LATE ictal spread. The oscillatory changes can help visualize connectivity within the seizure network.

Hemispheric malformations of cortical development: surgical indications and approach.

INTRODUCTION: The term "hemispheric malformation of cortical development" (MCD) has come into the medical lexicon in the past 20 years as improvements and availability of advanced imaging techniques have permitted more precise diagnosis of a variety of brain developmental disorders that affect large regions of brain. These conditions are united by their propensity to elicit seizures that are difficult to control with medication in the children who suffer them. PURPOSE: The goal of surgical intervention is always to achieve seizure freedom and thereby give the affected child the best possible hope for neurological development. Even when seizure freedom cannot be achieved, a reduction in seizure burden is necessary to permit the survival of the child in many cases of MCD. EVALUATION: A presurgical evaluation of a patient presenting with severe epilepsy and a possible hemispheric malformation can be divided into three stages. The first includes an evaluation of available imaging, clinical, and genetic data to accurately diagnose the child and help determine if surgical intervention is an option. The next includes an evaluation of EEG and neurological data, although this has limited utility in many clinical circumstances. Finally, a clinical team must decide upon an appropriate surgical strategy among a variety of options. CONCLUSIONS: In this review, we will examine the set of diagnoses and associated imaging characteristics that describe the set of conditions for which surgical intervention is a possibility. We include a discussion of available surgical options, describing our own experience with surgery for MCD and the associated postoperative considerations including rates of seizure freedom, considerations for reoperation, and hydrocephalus.

Neuronal activity in the human subthalamic nucleus encodes decision conflict during action selection.

The subthalamic nucleus (STN), which receives excitatory inputs from the cortex and has direct connections with the inhibitory pathways of the basal ganglia, is well positioned to efficiently mediate action selection. Here, we use microelectrode recordings captured during deep brain stimulation surgery as participants engage in a decision task to examine the role of the human STN in action selection. We demonstrate that spiking activity in the STN increases when participants engage in a decision and that the level of spiking activity increases with the degree of decision conflict. These data implicate the STN as an important mediator of action selection during decision processes.