Therapeutic approaches targeting seizure networks.

Epilepsy is one of the most common neurological disorders, affecting over 65 million people worldwide. Despite medical management with anti-seizure medications (ASMs), many patients fail to achieve seizure freedom, with over one-third of patients having drug-resistant epilepsy (DRE). Even with surgical management through resective surgery and/or neuromodulatory interventions, over 50 % of patients continue to experience refractory seizures within a year of surgery. Over the past 2 decades, studies have increasingly suggested that treatment failure is likely driven by untreated components of a pathological seizure network, a shift in the classical understanding of epilepsy as a focal disorder. However, this shift in thinking has yet to translate to improved treatments and seizure outcomes in patients. Here, we present a narrative review discussing the process of surgical epilepsy management. We explore current surgical interventions and hypothesized mechanisms behind treatment failure, highlighting evidence of pathologic seizure networks. Finally, we conclude by discussing how the network theory may inform surgical management, guiding the identification and targeting of more appropriate surgical regions. Ultimately, we believe that adapting current surgical practices and neuromodulatory interventions towards targeting seizure networks offers new therapeutic strategies that may improve seizure outcomes in patients suffering from DRE.

Current Status of Awake Spine Surgery: A Bibliometric Analysis.

BACKGROUND: Spine surgery accounts for a large proportion of neurosurgical procedures, with approximately 313 million spine surgeries conducted annually worldwide. Considering delayed recovery and postoperative complications that are commonly reported, there has been a recent shift toward minimally invasive spine procedures conducted under local anesthesia. Despite proven success, there exists a limited body of literature on the use of awake surgery in spinal procedures. METHODS: A bibliometric analysis was conducted to map the current landscape of work in this field. 190 articles were identified from the Web of Science (Clarivate, NY) database. A comprehensive bibliometric analysis was performed on a narrowed list of the most relevant articles using Bibliometrix, an R-based programming tool. RESULTS: There has been a rise in academic papers published on the topic of awake spine surgery since 2016, with an increase in publication count by approximately 18% annually and each article cited approximately ten times on average to date. The year 2022 saw an uptick in publications, with 9 throughout the entire year. The most impactful article, with a total of 95 citations, was published by Sairyo et al.1 Thematic analysis revealed that the terms "lumbar spine" and "stenosis" are well-developed topics in the literature, whereas the topics of "complications," "fusion," and "cost-analysis" are less well-developed topics. CONCLUSIONS: This study provides a comprehensive overview of the most-cited articles in the field of awake spine surgery. Specifically, it identifies areas that are well represented in the literature and those which are underrepresented and should be areas of continued future research.

Modeling seizure networks in neuron-glia cultures using microelectrode arrays.

Epilepsy is a common neurological disorder, affecting over 65 million people worldwide. Unfortunately, despite resective surgery, over 30 % of patients with drug-resistant epilepsy continue to experience seizures. Retrospective studies considering connectivity using intracranial electrocorticography (ECoG) obtained during neuromonitoring have shown that treatment failure is likely driven by failure to consider critical components of the seizure network, an idea first formally introduced in 2002. However, current studies only capture snapshots in time, precluding the ability to consider seizure network development. Over the past few years, multiwell microelectrode arrays have been increasingly used to study neuronal networks in vitro. As such, we sought to develop a novel in vitro MEA seizure model to allow for study of seizure networks. Specifically, we used 4-aminopyridine (4-AP) to capture hyperexcitable activity, and then show increased network changes after 2 days of chronic treatment. We characterize network changes using functional connectivity measures and a novel technique using dimensionality reduction. We find that 4-AP successfully captures persistently elevated mean firing rate and significant changes in underlying connectivity patterns. We believe this affords a robust in vitro seizure model from which longitudinal network changes can be studied, laying groundwork for future studies exploring seizure network development.

A Mouse Model of Temporal Lobe Contusion.

Trauma to the brain can induce a contusion characterized by a discrete intracerebral or diffuse interstitial hemorrhage. In humans, "computed tomography-positive," that is, hemorrhagic, temporal lobe contusions (tlCont) have unique sequelae. TlCont confers significantly increased odds for moderate or worse disability and the inability to return to baseline work capacity compared to intra-axial injuries in other locations. Patients with tlCont are at elevated risks of memory dysfunction, anxiety, and post-traumatic epilepsy due to involvement of neuroanatomical structures unique to the temporal lobe including the amygdala, hippocampus, and ento-/perirhinal cortex. Because of the relative inaccessibility of the temporal lobe in rodents, no preclinical model of tlCont has been described, impeding progress in elucidating the specific pathophysiology unique to tlCont. Here, we present a minimally invasive mouse model of tlCont with the contusion characterized by a traumatic interstitial hemorrhage. Mortality was low and sensorimotor deficits (beam walk, accelerating rotarod) resolved completely within 3-5 days. However, significant deficits in memory (novel object recognition, Morris water maze) and anxiety (elevated plus maze) persisted at 14-35 days and nonconvulsive electroencephalographic seizures and spiking were significantly increased in the hippocampus at 7-21 days. Immunohistochemistry showed widespread astrogliosis and microgliosis, bilateral hippocampal sclerosis, bilateral loss of hippocampal and cortical inhibitory parvalbumin neurons, and evidence of interhemispheric connectional diaschisis involving the fiber bundle in the ventral corpus callosum that connects temporal lobe structures. This model may be useful to advance our understanding of the unique features of tlCont in humans.

Introducing FCR6-Brain: Measuring fear of cancer recurrence in brain tumor patients and their caregivers.

Background: Fear of cancer recurrence (FCR) is a psychological consequence of cancer diagnosis that impacts quality of life in neuro-oncology. However, the instruments used to assess FCR have not been tested for validity in patients with brain tumors. The present study explored the psychometric properties of a brief FCR scale in patients with primary brain tumor (PBT) and their caregivers. Methods: Adult patients with PBT (n = 165) and their caregivers (n = 117) completed the FCR-7-item scale (FCR7) and measures of psychological functioning. Exploratory factor analyses (EFA) were conducted for both patient and caregiver FCR7. Convergent validity, prevalence, the difference between FCR in patients and caregivers, and relationships with relevant medical and demographic variables were explored. Results: EFAs revealed a single factor with one item demonstrating poor loading for both patients and caregivers. Removal of the item measuring hypervigilance symptoms (checking for physical signs of tumor) greatly improved the single factor metrics. The amended scale (FCR6-Brain) demonstrated good convergent validity. Caregiver FCR was significantly higher than patient. Clinical guidance to identify clinically significant FCR was introduced. Age, gender, and time since diagnosis were related to FCR, with higher FCR in younger women more recently diagnosed. Conclusions: The FCR6-Brain is the first validated instrument to assess FCR in this population and should be used to identify individuals at risk for FCR and guide development of future psychotherapeutic interventions. This study highlights the distinct characteristics of FCR in neuro-oncology. Symptoms of hypervigilance in PBT patients need further investigation.