Search

Brain aging contributes to cognitive decline and risk of dementia. Degeneration of the basal forebrain cholinergic system parallels these changes in aging, Alzheimer's dementia, Parkinson's dementia, and Lewy body dementia, and thus is a common element linked to executive function across the lifespan and in disease states. Here, we tested the potential of one-hour daily intermittent basal forebrain stimulation to improve cognition in senescent monkeys, and its mechanisms of action. Stimulation in five animals improved working memory duration in 8-12 weeks across all animals, with peak improvements observed in the first four weeks. In an ensuing three month period without stimulation, improvements were retained. With additional stimulation, performance remained above baseline throughout the 15 months of the study. Studies with a cholinesterase inhibitor produced inconsistent improvements in behavior. One of five animals improved significantly. Manipulating the stimulation pattern demonstrated selectivity for both stimulation and recovery period duration. Brain stimulation led to acute increases in cerebrospinal levels of tissue plasminogen activator, which is an activating element for two brain neurotrophins, Nerve Growth Factor (NGF) and Brain-Derived Growth Factor (BDNF). Stimulation also led to improved glucose utilization in stimulated hemispheres relative to contralateral. Glucose utilization also consistently declines with aging and some dementias. Together, these findings suggest that intermittent stimulation of the nucleus basalis of Meynert improves executive function and reverses some aspects of brain aging., Highlights: The basal forebrain and its cholinergic projections are the sole source of acetylcholine for the cortical mantle in primates and humans.Forebrain function tracks cognitive loss throughout the adult lifespan.One hour per day intermittent stimulation of this region improves executive function behaviors and plausibly reverses some aspects of brain aging, a large risk factor in dementias.This stimulation exceeds impacts of standard pharmacotherapies, is enduring, recruits brain neurotrophic pathways and improves cortical glucose utilization.

Background: Outcomes after surgical treatment of chronic subdural hematoma (cSDH) remain undesirable in a significant proportion of patients. We aimed to show the role of middle meningeal artery (MMA) embolization and to demonstrate its benefits., Methods: Thirty-five patients with symptomatic cSDH were enrolled in a prospective randomized trial following evacuation surgery. Participants were randomized to embolization or control group (expectant management following surgical evacuation without embolization). Patients were followed throughout their hospitalization and outpatient follow-ups. The main goals of this planned interim analysis were to assess neurological outcome and resource utilization., Results: The groups were comparable in terms of sex, age and follow-up retention rates. Side(s) of intervention(s) and hematoma size were similar. There was no statistical difference in neurological examination improvement at discharge, but at follow-up, we observed a decline in neurologic exam in the control group (p = 0.03). Control group participants required more re-interventions (p = 0.02) and were followed in clinic and during related readmissions for longer (p = 0.02). The number of imaging studies obtained in relation to the disease management was higher in the control group (p = 0.01)., Conclusions: Our results suggest a beneficial role for the addition of MMA embolization to surgical intervention in the treatment of symptomatic chronic subdural hematoma. Neurological outcomes were significantly better in the embolization group. This contributed to less need for follow-up, re-interventions, and imaging studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Traumatic brain injury (TBI) is one of the foremost causes of disability and mortality globally. While the scientific and medical emphasis is to save lives and avoid disability during acute period of injury, a severe health problem can manifest years after injury. For instance, TBI increases the risk of cognitive impairment in the elderly. Remote TBI history was reported to be a cause of the accelerated clinical trajectory of Alzheimer's disease-related dementia (ADRD) resulting in earlier onset of cognitive impairment and increased AD-associated pathological markers like greater amyloid deposition and cortical thinning. It is not well understood whether a single TBI event may increase the risk of dementia. Moreover, the cellular signaling pathways remain elusive for the chronic effects of TBI on cognition. We have hypothesized that a single TBI induces sustained neuroinflammation and disrupts cellular communication in a way that results later in ADRD pathology. To test this, we induced TBI in young adult CD1 mice and assessed the behavioral outcomes after 11 months followed by pathological, histological, transcriptomic, and MRI assessment. On MRI scans, these mice showed significant loss of tissue, reduced CBF, and higher white matter injury compared to sham mice. We found these brains showed progressive atrophy, markers of ADRD, sustained astrogliosis, loss of neuronal plasticity, and growth factors even after 1-year post-TBI. Because of progressive neurodegeneration, these mice had motor deficits, showed cognitive impairments, and wandered randomly in open field. We, therefore, conclude that progressive pathology after adulthood TBI leads to neurodegenerative conditions such as ADRD and impairs neuronal functions., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Background: Premature discontinuation and nonpublication of clinical trials contribute to research waste and compromise our ability to improve patient outcomes. However, the extent to which these problems exist in neurooncological randomized clinical trials (RCTs) is not known. This study aimed to evaluate the prevalence of discontinuation and nonpublication of neurooncological RCTs, identify contributing factors, and assess trial characteristics associated with each., Methods: We performed a retrospective, cross-sectional study of neurooncological RCTs registered in Clinicaltrials.gov before March 7, 2023. Data were collected from Clinicaltrials.gov and associated publications were located. We attempted to contact authors for all trials without associated publications or an identified reason for discontinuation., Results: Of 139 included RCTs, 57 (41%) were discontinued. The most common reason for discontinuation identified was slow enrollment or accrual (23%), though 30 trials (53%) were discontinued for unknown reasons. Trials funded by sources other than industry or the National Institutes of Health were more likely to be discontinued (odds ratio 4.2, 95% confidence interval 1.3-13.8). In total, 67 of the 139 (48%) RCTs were unpublished, including 50 of the 57 (88%) discontinued studies and 17 of the 82 (21%) completed studies., Conclusions: In our study, discontinuation of neurooncological clinical trials was common and often occurred for unknown reasons. Trials were also frequently unpublished, particularly those that were discontinued. Addressing these findings may provide an opportunity to reduce research waste and improve outcomes for patients with neurological cancers., Competing Interests: All authors: None declared., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Objective: The Open Payments Program (OPP) was a database started in 2013 by the US government to report payments made by the medical device and pharmaceutical industry to physicians. Neurosurgery is a technologically advanced field that relies heavily on the latest innovations for complex treatment of its patient population. This study sought to explore the financial relationship between academic neurosurgeons and the industry., Methods: OPP data were reviewed for the year 2021 of all faculty neurosurgeons affiliated with a neurosurgery residency program. Trends related to general payments, research payments, associated research funding, ownership and investment interest, name of the companies making payments, monetary amount of payments per company, and number of payments per company were analyzed., Results: Industry payments to 1151 US academic neurosurgeons were reviewed. These neurosurgeons received $121.4 million in payments. Three hundred thirty-two companies made 18,466 payments. The average payment per neurosurgeon was approximately six-fold higher than that of all other physicians. Vascular and spine subspecialties received the highest payments. A higher proportion of research money was allocated to the Pacific division, while all other categories (including total amount) were higher in the Eastern US. Most financial contributions were made by a small number of companies., Conclusions: Neurosurgery has been rated by many as a field fueled by research, innovation, and technology. In 2021, academic neurosurgeons had a strong relationship with the medical device and pharmaceutical industry as reflected in the OPP data. While the true impact on patient care cannot be directly measured, the advancement of the field relies heavily on these collaborations.

Background: Although endoscopic techniques have become more widespread in repair of frontal sinus (FS) defects, certain pathologies still require open approach (extensive trauma or tumors). Under certain circumstances even multiple complex open reconstructive procedures might fail to resolve persistent pneumocephalus or CSF leak and subsequently surgeons tend to escalate the invasiveness and employ even more complex and aggressive approaches. We present our experience treating persistent pneumocephalus or CSF leak after previously failed transcranial reconstruction utilizing an endoscopic endonasal approach (EEA)., Methods: We retrospectively reviewed a prospectively maintained database of all patients undergoing an EEA for repair of persistent pneumocephalus or CSF leak following FS cranialization between 2016 and 2020., Results: Six patients who underwent cranialization of the FS with subsequent persistent pneumocephalus or CSF leak were identified; two patients suffered a traumatic fracture of the FS, remaining four patients had undergone previous cranial surgery. Clear violation of the FS was not recognized in one patient. All patients underwent cranialization of the FS either directly following initial craniotomy or during open repair of a FS fracture. Two patients underwent multiple transcranial surgeries including using vascularized free tissue transfer. Complete cessation of pneumocephalus/CSF leak was achieved in 83.3% (5/6) after the first and 100% (6/6) after two endoscopic procedures. No morbidity or mortality resulted from the endoscopic procedure., Conclusions: Skull base defects following a failed cranialization of FS are usually located in or in close proximity to the frontal recess. These defects can be safely and effectively repaired via an EEA.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes persistent synovitis, bone damage, and progressive joint destruction. Neuroimmune modulation through electrical stimulation of the vagus nerve activates the inflammatory reflex and has been shown to inhibit the production and release of inflammatory cytokines and decrease clinical signs and symptoms in RA. The RESET-RA study was designed to determine the safety and efficacy of an active implantable device for treating RA., Methods: The RESET-RA study is a randomized, double-blind, sham-controlled, multi-center, two-stage pivotal trial that enrolled patients with moderate-to-severe RA who were incomplete responders or intolerant to at least one biologic or targeted synthetic disease-modifying anti-rheumatic drug. A neuroimmune modulation device (SetPoint Medical, Valencia, CA) was implanted on the left cervical vagus nerve within the carotid sheath in all patients. Following post-surgical clearance, patients were randomly assigned (1:1) to active stimulation or non-active (control) stimulation for 1 min once per day. A predefined blinded interim analysis was performed in patients enrolled in the study's initial stage (Stage 1) that included demographics, enrollment rates, device implantation rates, and safety of the surgical procedure, device, and stimulation over 12 weeks of treatment., Results: Sixty patients were implanted during Stage 1 of the study. All device implant procedures were completed without intraoperative complications, infections, or surgical revisions. No unanticipated adverse events were reported during the perioperative period and at the end of 12 weeks of follow-up. No study discontinuations were due to adverse events, and no serious adverse events were related to the device or stimulation. Two serious adverse events were related to the implantation procedure: vocal cord paresis and prolonged hoarseness. These were reported in two patients and are known complications of surgical implantation procedures with vagus nerve stimulation devices. The adverse event of vocal cord paresis resolved after vocal cord augmentation injections with filler and speech therapy. The prolonged hoarseness had improved with speech therapy, but mild hoarseness persists., Conclusions: The surgical procedures for implantation of the novel neuroimmune modulation device for the treatment of RA were safe, and the device and its use were well tolerated., Trial Registration: NCT04539964; August 31, 2020., (© 2024. The Author(s).)

The role of resting state functional MRI (rsfMRI) is increasing in the field of epilepsy surgery because it is possible to interpolate network connectivity patterns across the brain with a high degree of spatial resolution. Prior studies have shown that by rsfMRI with scalp electroencephalography (EEG), an epileptogenic network can be modeled and visualized with characteristic patterns of connectivity that are relevant to both seizure-related and neuropsychological outcomes after surgery. The aim of this study is to show that a 5-min acquisition time provides reproducible results related to the relevant connectivity metrics when compared to a separately acquired 5-min scan. Fourteen separate rsfMRI sessions from ten different patients were used for comparison, comprised of patients with temporal lobe epilepsy both pre- and post-operation. Results showed that there was no significant difference in any of the connectivity metrics when comparing both 5-min scans to each other. These data support the continued use of a 5-min scan for epileptogenic network modeling in future studies because the inter-scan variability is sufficiently low as not to alter the output metrics characterizing the network connectivity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Neal, Schimmel, George, Monsour, Alayli, Lockard, Piper, Maciver, Vale and Bezchlibnyk.)

Background: Epilepsy, a disease characterized by recurrent seizures, is a common chronic neurologic condition. Antiepileptic drugs (AED) are the mainstay of treatment for epilepsy. Vagus nerve stimulation (VNS) surgery is an adjuvant therapy for the treatment of drug refractory epilepsy (DRE). VNS revision and implant removal surgeries remain common., Methods: Using a single neurosurgeon data registry for epilepsy surgery, we retrospectively analyzed a total of 824 VNS surgeries. Patients were referred to two Level IV Comprehensive Epilepsy centers (from 08/1997 to 08/2022) for evaluation. Patients were divided into four groups: new device placement, revision surgery, removal surgery, and battery replacement for end-of-life of the generator. The primary endpoint was to analyze the reasons that led patients to undergo revision and removal surgeries. The time period from the index surgery to the removal surgery was also calculated., Results: The median age of patients undergoing any type of surgery was 34 years. The primary reason for revision surgeries was device malfunction, followed by patients' cosmetic dissatisfaction. There was no statistical sex-difference in revision surgeries. The median age and body mass index (BMI) of patients who underwent revision surgery were 38 years and 26, respectively. On the other hand, the primary reason for removal was lack of efficacy, followed again by cosmetic dissatisfaction. The survival analysis showed that 43% of VNS device remained in place for 5 years and 50% of the VNS devices were kept for 1533 days or 4.2 years., Conclusions: VNS therapy is safe and well-tolerated. VNS revision and removal surgeries occur in less than 5% of cases. More importantly, attention to detail and good surgical technique at the time of the index surgery can increase patient satisfaction, minimize the need for further surgeries, and improve acceptance of the VNS technology., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative to surgical resection for drug-resistant mesial temporal lobe epilepsy (mTLE). Reported rates of seizure freedom are variable and long-term durability is largely unproven. Anterior temporal lobectomy (ATL) remains an option for patients with MRgLITT treatment failure. However, the safety and efficacy of this staged strategy is unknown., Methods: This multicentre, retrospective cohort study included 268 patients consecutively treated with mesial temporal MRgLITT at 11 centres between 2012 and 2018. Seizure outcomes and complications of MRgLITT and any subsequent surgery are reported. Predictive value of preoperative variables for seizure outcome was assessed., Results: Engel I seizure freedom was achieved in 55.8% (149/267) at 1 year, 52.5% (126/240) at 2 years and 49.3% (132/268) at the last follow-up ≥1 year (median 47 months). Engel I or II outcomes were achieved in 74.2% (198/267) at 1 year, 75.0% (180/240) at 2 years and 66.0% (177/268) at the last follow-up. Preoperative focal to bilateral tonic-clonic seizures were independently associated with seizure recurrence. Among patients with seizure recurrence, 14/21 (66.7%) became seizure-free after subsequent ATL and 5/10 (50%) after repeat MRgLITT at last follow-up≥1 year., Conclusions: MRgLITT is a viable treatment with durable outcomes for patients with drug-resistant mTLE evaluated at a comprehensive epilepsy centre. Although seizure freedom rates were lower than reported with ATL, this series represents the early experience of each centre and a heterogeneous cohort. ATL remains a safe and effective treatment for well-selected patients who fail MRgLITT., Competing Interests: Competing interests: Several centres that contributed data to this study are sites in the ongoing Stereotactic Laser Ablation for Temporal Lobe Epilepsy (SLATE) study (NCT02844465) sponsored by Medtronic (Minneapolis, Minnesota, USA). Procedures reported here precede any enrolment in SLATE. This study was not industry sponsored. AS is Chief Medical Officer of Medtronic Neuromodulation Operating Unit., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Endocannabinoids [2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)], endogenously produced arachidonate-based lipids, are anti-inflammatory physiological ligands for two known cannabinoid receptors, CB1 and CB2, yet the molecular and cellular mechanisms underlying their effects after brain injury are poorly defined. In the present study, we hypothesize that traumatic brain injury (TBI)-induced loss of endocannabinoids exaggerates neurovascular injury, compromises brain-cerebrospinal fluid (CSF) barriers (BCB) and causes behavioral dysfunction. Preliminary analysis in human CSF and plasma indicates changes in endocannabinoid levels. This encouraged us to investigate the levels of endocannabinoid-metabolizing enzymes in a mouse model of controlled cortical impact (CCI). Reductions in endocannabinoid (2-AG and AEA) levels in plasma were supported by higher expression of their respective metabolizing enzymes, monoacylglycerol lipase (MAGL), fatty acid amide hydrolase (FAAH), and cyclooxygenase 2 (Cox-2) in the post-TBI mouse brain. Following increased metabolism of endocannabinoids post-TBI, we observed increased expression of CB2, non-cannabinoid receptor Transient receptor potential vanilloid-1 (TRPV1), aquaporin 4 (AQP4), ionized calcium binding adaptor molecule 1 (IBA1), glial fibrillary acidic protein (GFAP), and acute reduction in cerebral blood flow (CBF). The BCB and pericontusional cortex showed altered endocannabinoid expressions and reduction in ventricular volume. Finally, loss of motor functions and induced anxiety behaviors were observed in these TBI mice. Taken together, our findings suggest endocannabinoids and their metabolizing enzymes play an important role in the brain and BCB integrity and highlight the need for more extensive studies on these mechanisms., Competing Interests: Declaration of Competing Interest Authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We present an experimental protocol to record neuronal activity during intermittent stimulation of nucleus basalis (NB), as macaque monkeys perform cognitive tasks. This protocol includes implantation of electrodes and generator devices to deliver electrical stimulation to NB using multiple approaches in monkeys. Direct stimulation of NB avoids peripheral cholinergic side effects, optimizes timing, and activates non-cholinergic projection neurons. We describe electrode preparation, surgery, and implantation for direct evaluation of how stimulation affects monkeys' behavior and neuronal activity. For complete details on the use and execution of this profile, please refer to Qi et al. (2021)., Competing Interests: The authors have received stimulator devices from Boston Scientific through a Materials Transfer Agreement., (© 2022 The Authors.)

Mitochondria are dynamic organelles responsible for cellular energy production. Besides, regulating energy homeostasis, mitochondria are responsible for calcium homeostasis, signal transmission, and the fate of cellular survival in case of injury and pathologies. Accumulating reports have suggested multiple roles of mitochondria in neuropathologies, neurodegeneration, and immune activation under physiological and pathological conditions. Mitochondrial dysfunction, which occurs at the initial phase of brain injury, involves oxidative stress, inflammation, deficits in mitochondrial bioenergetics, biogenesis, transport, and autophagy. Thus, development of targeted therapeutics to protect mitochondria may improve functional outcomes following traumatic brain injury (TBI) and intracerebral hemorrhages (ICH). In this review, we summarize mitochondrial dysfunction related to TBI and ICH, including the mechanisms involved, and discuss therapeutic approaches with special emphasis on past and current clinical trials., (Published by Elsevier Ltd.)

Objective: The aim of this study was to define the structural relationship between the arcuate eminence (AE) and a known fixed external bony landmark, the root of the zygoma (ZR), and to determine its reliability as a consistent guide for guiding surgical approaches. To our knowledge, this is the only anatomic study to quantify the relationship between the AE and ZR., Methods: Twenty-one dry temporal bones were measured using digital calipers. The distance from the posterior aspect of the ZR to the midpoint of the AE was measured. Additionally, the anteroposterior distance between the ZR and AE and vertical distance between the 2 structures were measured. Student's t-test was used to compare the left and right sides., Results: An AE was found in every specimen. The mean ZR to AE distance was 30.9 mm. On most sides (91%), the ZR was located more inferiorly than the AE with a mean distance of 3 mm between the 2 structures. The mean distance between the AE and ZR was 17 mm. On all sides, the AE was located posterior to the ZR. No significant differences were found between sides. No anatomic variations or pathologic conditions were noted in any of the specimens., Conclusions: The ZR is an easily identifiable and consistent bony landmark often used by skull base surgeons. In this investigation, we measured the anatomic relationships between the ZR and AE. Such data might assist in planning surgical trajectories and minimizing complications when skull base pathologies are approached., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Brain regions positively correlated with the epileptogenic zone in patients with temporal lobe epilepsy vary in spread across the brain and in the degree of correlation to the temporal lobes, thalamus, and limbic structures, and these parameters have been associated with pre-operative cognitive impairment and seizure freedom after epilepsy surgery, but negatively correlated regions have not been as well studied. We hypothesize that connectivity within a negatively correlated epilepsy network may predict which patients with temporal lobe epilepsy will respond best to surgery. Methods: Scalp EEG and resting state functional MRI (rsfMRI) were collected from 19 patients with temporal lobe epilepsy and used to estimate the irritative zone. Using patients' rsfMRI, the negatively correlated epilepsy network was mapped by determining all the brain voxels that were negatively correlated with the voxels in the epileptogenic zone and the spread and average connectivity within the network was determined. Results: Pre-operatively, connectivity within the negatively correlated network was inversely related to the spread (diffuseness) of that network and positively associated with higher baseline verbal and logical memory. Pre-operative connectivity within the negatively correlated network was also significantly higher in patients who would go on to be seizure free. Conclusion: Patients with higher connectivity within brain regions negatively correlated with the epilepsy network had higher baseline memory function, narrower network spread, and were more likely to be seizure free after surgery., Competing Interests: EN and FV are inventors and hold a US patent (#10,588,561) for the network modeling algorithm used in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Neal, Schoenberg, Maciver, Bezchlibnyk and Vale.)

The CNS is regarded as an immunoprivileged organ, evading routine immune surveillance; however, the coordinated development of immune responses profoundly influences outcomes after brain injury. Innate lymphoid cells (ILCs) are cytokine-producing cells that are critical for the initiation, modulation, and resolution of inflammation, but the functional relevance and mechanistic regulation of ILCs are unexplored after acute brain injury. We demonstrate increased proliferation of all ILC subtypes within the meninges for up to 1 year after experimental traumatic brain injury (TBI) while ILCs were present within resected dura and elevated within cerebrospinal fluid (CSF) of moderate-to-severe TBI patients. In line with energetic derangements after TBI, inhibition of the metabolic regulator, AMPK, increased meningeal ILC expansion, whereas AMPK activation suppressed proinflammatory ILC1/ILC3 and increased the frequency of IL-10-expressing ILC2 after TBI. Moreover, intracisternal administration of IL-33 activated AMPK, expanded ILC2, and suppressed ILC1 and ILC3 within the meninges of WT and Rag1-/- mice, but not Rag1-/- IL2rg-/- mice. Taken together, we identify AMPK as a brake on the expansion of proinflammatory, CNS-resident ILCs after brain injury. These findings establish a mechanistic framework whereby immunometabolic modulation of ILCs may direct the specificity, timing, and magnitude of cerebral immunity.

Studying the complex molecular mechanisms involved in traumatic brain injury (TBI) is crucial for developing new therapies for TBI. Current treatments for TBI are primarily focused on patient stabilization and symptom mitigation. However, the field lacks defined therapies to prevent cell death, oxidative stress, and inflammatory cascades which lead to chronic pathology. Little can be done to treat the mechanical damage that occurs during the primary insult of a TBI; however, secondary injury mechanisms, such as inflammation, blood-brain barrier (BBB) breakdown, edema formation, excitotoxicity, oxidative stress, and cell death, can be targeted by therapeutic interventions. Elucidating the many mechanisms underlying secondary injury and studying targets of neuroprotective therapeutic agents is critical for developing new treatments. Therefore, we present a review on the molecular events following TBI from inflammation to programmed cell death and discuss current research and the latest therapeutic strategies to help understand TBI-mediated secondary injury.

Cannabis-inspired medical products are garnering increasing attention from the scientific community, general public, and health policy makers. A plethora of scientific literature demonstrates intricate engagement of the endocannabinoid system with human immunology, psychology, developmental processes, neuronal plasticity, signal transduction, and metabolic regulation. Despite the therapeutic potential, the adverse psychoactive effects and historical stigma, cannabinoids have limited widespread clinical application. Therefore, it is plausible to weigh carefully the beneficial effects of cannabinoids against the potential adverse impacts for every individual. This is where the concept of "personalized medicine" as a promising approach for disease prediction and prevention may take into the account. The goal of this review is to provide an outline of the endocannabinoid system, including endocannabinoid metabolizing pathways, and will progress to a more in-depth discussion of the therapeutic interventions by endocannabinoids in various neurological disorders., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© European Association for Predictive, Preventive and Personalised Medicine (EPMA) 2020.)

Background: Patients with a lesion within the amygdala and uncus may develop temporal lobe epilepsy despite having functional mesial structures. Resection of functional hippocampus and surrounding structures may lead to unacceptable iatrogenic deficits. To our knowledge, there is limited descriptions of surgical techniques for selectively resecting the amygdala and uncus lesions while preserving the hippocampus in patients with language-dominant temporal lobe pathology., Methods: Thirteen patients with language-dominant temporal lobe epilepsy related to amygdala-centric lesions were identified. Patients with sclerosis of the mesial structures or evidence of pathology outside of the amygdala-uncus region were excluded. Neuropsychological evaluation confirmed normal function of the mesial structures ipsilateral to the lesion. All patients were worked up with video-EEG, high-resolution brain MRI, neuro-psychology evaluation, and either Wada or functional MRI testing., Results: All patients underwent selective resection of the lesion including amygdala and uncus with preservation of the hippocampus via a transcortical inferior temporal gyrus approach to the mesial temporal lobe. Pathology was compatible with glioneuronal tumors. Post-operative MRI demonstrated complete resection in all patients. Eight of the thirteen patients underwent post-operative neuropsychology evaluations and did not demonstrate any significant decline in tasks of delayed verbal recall or visual memory based on the Rey Auditory Verbal Learning Test (RAVLT). One patient showed a slight decrease in confrontation naming using the Boston Naming Test (BNT). Seizure freedom (Engel class I) was achieved in 12 of 13 patients., Conclusion: Selective transcortical amygdala and uncus resection with hippocampus preservation may be a reasonable way to achieve seizure control while sparing functional mesial structures.

Purpose: A novel software algorithm combining non-invasive EEG and resting state functional MRI data to map networks of cortex correlated to epileptogenic tissue was used to map an epilepsy network non-invasively. The relationship between epilepsy network connectivity and outcomes after surgery was investigated using this non-invasive and non-concurrent modeling algorithm., Method: Scalp EEG and resting state functional MRI were acquired for nineteen patients with temporal lobe epilepsy. The hypothetical irritative zone was mapped, and resting state functional MRI data was used to model regions functionally correlated with the irritative zone. Epilepsy network connectivity was measured in patient with temporal lobe epilepsy (n = 19) both pre- and post-operatively. Temporal networks were also mapped in healthy control participants (n = 6)., Results: Thirteen of nineteen patients (68 %) were seizure free after 20.3 ± 4.8 months. Epilepsy network connectivity within the temporal lobe was significantly higher among patients with temporal lobe epilepsy compared to the healthy control patients (p < 0.05). Disconnection of the epilepsy network was significantly higher in patients who were seizure free. Using spearman rho analyses, neuropsychological function after surgery was found to be relatively better in patients with higher degree of epilepsy network disconnection., Conclusions: The magnitude of network disconnection after surgery was strongly associated with increased rates of seizure freedom and relatively better neuropsychological measures of memory and naming function. It was shown that seizure-free outcomes and relatively improved neuropsychological function correlated with surgical disconnection of a highly synchronous epilepsy network., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Introduction: Surgery remains an essential option for the treatment of medically intractable temporal lobe epilepsy (TLE). However, only 66% of patients achieve postoperative seizure freedom, perhaps attributable to an incomplete understanding of brain network alterations in surgical candidates. Here, we applied a novel network modeling algorithm and measured key characteristics of epileptic networks correlated with surgical outcomes and objective measures of cognition., Methods: Twenty-two patients were prospectively included, and relevant demographic information was attained. Resting state functional magnetic resonance imaging (rsfMRI) and electroencephalography (EEG) data were recorded and preprocessed. Using our novel algorithm, patient-specific epileptic networks were mapped preoperatively, and geographic spread was quantified. Global functional connectivity was also determined using a volumetric functional atlas. Neuropsychological pre- and postsurgical raw and standardized scores obtained blinded to epileptic network status. Key demographic data and features of epileptic networks were then correlated with surgical outcome using Pearson's product-moment correlation., Results: At an average follow-up of 18.4 months, 15/22 (68%) patients were seizure-free. Connectivity was measured globally using a functional 3D atlas. Higher mean global connectivity correlated with worse scores in preoperative neuropsychological testing of executive functioning (Ruff Figural Fluency Test [RFFT]-ER; R = 0.943, p = 0.005). A higher ratio of highly correlated connections between regions of interest (ROIs) in the hemisphere contralateral to the seizure onset correlated with impairment in executive functioning (RFFT-ER; R = 0.943, p = 0.005). Higher numbers of highly correlated connections between ROIs in the contralateral hemisphere correlated with impairment in both short- and long-term measures of verbal memory (Rey Auditory Verbal Learning Test Trials 6, 7 [RAVLT6, RAVLT7]; R = -0.650, p = 0.020, R = -0.676, p = 0.030). Epilepsy networks were modeled in each patient, and localization of the epilepsy network in the bitemporal lobes correlated with lower scores in neuropsychological tests measuring verbal learning and short-term memory (RAVLT6; R = -0.671, p = 0.024). Higher rates of seizure recurrence correlated with localization of the epilepsy network bitemporally (R = -0.542, p = 0.014), with the stronger correlation found with localization to the contralateral temporal lobe from side of surgery (R = - 0.530, p = 0.016)., Conclusion: Increased connectivity contralateral to seizure onset and epilepsy network spread in the bitemporal lobes correlated with lower measures of executive functioning and verbal memory. Epilepsy network localization to the bitemporal lobes, in particular, the contralateral temporal lobe, is associated with higher rates of seizure recurrence. These findings may reflect network-level disruption that has infiltrated the contralateral hemisphere and the bitemporal lobes contributing to impaired cognition and relatively worse surgical outcomes. Further identification of network parameters that predict patient outcomes may aid in patient selection, resection planning, and ultimately the efficacy of epilepsy surgery., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) has reported seizure freedom rates between 36% and 78% with at least 1 year of follow-up. Unfortunately, the lack of robust methods capable of incorporating the inherent variability of patient anatomy, the variability of the ablated volumes, and clinical outcomes have limited three-dimensional quantitative analysis of surgical targeting and its impact on seizure outcomes. We therefore aimed to leverage a novel image-based methodology for normalizing surgical therapies across a large multicenter cohort to quantify the effects of surgical targeting on seizure outcomes in LITT for mTLE., Methods: This multicenter, retrospective cohort study included 234 patients from 11 centers who underwent LITT for mTLE. To investigate therapy location, all ablation cavities were manually traced on postoperative magnetic resonance imaging (MRI), which were subsequently nonlinearly normalized to a common atlas space. The association of clinical variables and ablation location to seizure outcome was calculated using multivariate regression and Bayesian models, respectively., Results: Ablations including more anterior, medial, and inferior temporal lobe structures, which involved greater amygdalar volume, were more likely to be associated with Engel class I outcomes. At both 1 and 2 years after LITT, 58.0% achieved Engel I outcomes. A history of bilateral tonic-clonic seizures decreased chances of Engel I outcome. Radiographic hippocampal sclerosis was not associated with seizure outcome., Significance: LITT is a viable treatment for mTLE in patients who have been properly evaluated at a comprehensive epilepsy center. Consideration of surgical factors is imperative to the complete assessment of LITT. Based on our model, ablations must prioritize the amygdala and also include the hippocampal head, parahippocampal gyrus, and rhinal cortices to maximize chances of seizure freedom. Extending the ablation posteriorly has diminishing returns. Further work is necessary to refine this analysis and define the minimal zone of ablation necessary for seizure control., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Objective: To determine the rate of hormone replacement therapy (HRT) after transsphenoidal surgery (TSS) for pituitary apoplexy (PA) versus elective resection of a null cell (NC) macroadenoma. Methods: A retrospective cohort study was performed. Data was collected on all consecutive patients who underwent TSS from December 31, 2000 to December 31, 2016. Patients were split into two groups: ( 1 ) patients that presented with PA, and ( 2 ) patients that underwent elective TSS for NC macroadenoma. Postoperative pituitary function was determined by examining HRT, hormone lab values, and an evaluation by an endocrinologist for each patient. The odds ratio (OR) was calculated to determine if there was an association between PA and the need for HRT after surgery when compared to elective resection of a NC macroadenoma. Results: The need for HRT was significantly higher following surgery for PA compared to resection of a NC macroadenoma (14.7% versus 2.9%, OR = 5.690; 95% confidence interval (CI) = 1.439 to 22.500; P = .013). Conclusion: There is an increased need for hormone replacement therapy after surgery in patients with PA versus patients undergoing elective resection of a NC macroadenoma. Further studies are warranted to strengthen this data and help determine further predictors of the need for HRT. Abbreviations: BNP = brain natriuretic peptide; CI = confidence interval; DDAVP = desmopressin acetate; GH = growth hormone; HRT = hormone replacement therapy; MRI = magnetic resonance imaging; NC = null cell (adenoma); OR = odds ratio; PA = pituitary apoplexy; TSS = transsphenoidal surgery.

Background: Laser interstitial thermal therapy (LITT) has recently gained popularity as a minimally invasive surgical option for the treatment of mesiotemporal epilepsy (mTLE). Similar to traditional open procedures for epilepsy, the most frequent neurological complications of LITT are visual deficits; however, a critical analysis of these injuries is lacking., Objectives: To evaluate the visual deficits that occur after LITT for mTLE and their etiology., Method: We surveyed five academic epilepsy centers that regularly perform LITT for cases of self-reported postoperative visual deficits. For these patients all pre-, intra- and postoperative MRIs were co-registered with an anatomic atlas derived from 7T MRI data. This was used to estimate thermal injury to early visual pathways and measure imaging variables relevant to the LITT procedure. Using logistic regression, we then compared 14 variables derived from demographics, mesiotemporal anatomy, and the surgical procedure for the patients with visual deficits to a normal cohort comprised of the first 30 patients to undergo this procedure at a single institution., Results: Of 90 patients that underwent LITT for mTLE, 6 (6.7%) reported a postoperative visual deficit. These included 2 homonymous hemianopsias (HHs), 2 quadrantanopsias, and 2 cranial nerve (CN) IV palsies. These deficits localized to the posterior aspect of the ablation, corresponding to the hippocampal body and tail, and tended to have greater laser energy delivered in that region than the normal cohort. The patients with HH had insult localized to the lateral geniculate nucleus, which was -associated with young age and low choroidal fissure CSF volume. Quadrantanopsia, likely from injury to the optic radiation in Meyer's loop, was correlated with a lateral trajectory and excessive energy delivered at the tail end of the ablation. Patients with CN IV injury had extension of contrast to the tentorial edge associated with a mesial laser trajectory., Conclusions: LITT for epilepsy may be complicated by various classes of visual deficit, each with distinct etiology and clinical significance. It is our hope that by better understanding these injuries and their mechanisms we can eventually reduce their occurrence by identifying at-risk patients and trajectories and appropriately tailoring the ablation procedure., (© 2020 S. Karger AG, Basel.)

For drug-resistant epilepsy, nonpharmacologic treatments should be considered early rather than late. Of the nondrug treatments, only resective surgery can be curative. Neurostimulation is palliative, i.e., not expected to achieve a seizure-free outcome. While resective surgery is the goal, other options are necessary because the majority of patients with drug-resistant epilepsy are not surgical candidates, and others have seizures that fail to improve with surgery or have only partial improvement but not seizure freedom. Neurostimulation modalities include vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS), each with its own advantages, disadvantages, and side effects. In most scenarios, determined by noninvasive evaluation, especially EEG and MRI, several strategies are reasonable. For focal epilepsies, the choices are between resective surgery, with or without intracranial EEG, and all three modalities of neurostimulation. In situations where resective surgery is likely to result in seizure freedom, such as mesiotemporal lobe epilepsy or lesional focal epilepsy, resection (standard, laser, or radiofrequency) is preferred. For difficult cases like extratemporal nonlesional epilepsies, neurostimulation offers a less invasive option than resective surgery. For generalized and multifocal epilepsies, VNS is an option, RNS is not, and DBS has only limited evidence. "This article is part of the Supplement issue Neurostimulation for Epilepsy.", (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: This study reports neuropsychological outcomes based on preoperative Wada testing in patients with drug-resistant mesial temporal lobe epilepsy (mTLE)., Methods: Patient records were retrospectively reviewed as part of a larger database. Patients with a diagnosis of TLE based on seizure semiology and long-term surface video-electroencephalography (EEG) were identified. These patients underwent preoperative and postoperative testing including advanced imaging (magnetic resonance imaging [MRI]), Wada testing, and neuropsychological assessment. Decrements in neuropsychological function were noted in comparison of pre- and postoperative studies. Patients had regular follow-up in the multidisciplinary epilepsy clinic to assess seizure outcomes. All participants had Engel class I/II outcome following selective amygdalohippocampectomy (AH) via the inferior temporal gyrus (ITG) approach., Results: Forty-eight patients with electrographic and clinical semiology consistent with unilateral mTLE were identified. Left mTLE was identified in 28 patients (58.3%), whereas 20 patients (41.7%) had right mTLE. Language-dominant hemisphere resections were performed on 23 patients (47.9%) (all left-sided surgery), whereas 25 (52.1%) had language nondominant resection (all right-sided and five left-sided surgery). Twenty-two participants (45.8%) showed no Wada memory asymmetry (No-WMA), whereas 26 (54.2%) exhibited Wada memory asymmetry (WMA). Postoperatively, analysis of variance (ANOVA) found that the No-WMA group exhibited a decline in verbal memory, but average scores on measures of nonverbal reasoning, general intelligence, and mood improved. Alternatively, patients with WMA did not show declines in memory postoperatively, and also exhibited improved nonverbal reasoning and general intelligence. Neither group exhibited reliable decline in verbal fluency or visual confrontation naming., Significance: Wada procedures for predicting surgical outcome from elective temporal surgery have been criticized and remain an area of active debate. However, decades of data across multiple epilepsy centers have demonstrated the value of Wada for reducing unanticipated neuropsychological adverse effects of surgical treatment. These data show that no Wada memory asymmetry increases the risk for neuropsychological decline following ITG approach for selective AH for drug-resistant mTLE.

Introduction: Primary neurological disorders are notoriously debilitating and deadly, and over the past four decades stem cell therapy has emerged as a promising treatment. Translation of stem cell therapies from the bench to the clinic requires a better understanding of delivery protocols, safety profile, and efficacy in each disease. Areas covered: In this review, benefits and risks of intracerebral stem cell transplantation are presented for consideration. Milestone discoveries in stem cell applications are reviewed to examine the efficacy and safety of intracerebral stem cell transplant therapy for disorders of the central nervous system and inform design of translatable protocols for clinically feasible stem cell-based treatments. Expert commentary: Intracerebral administration, compared to peripheral delivery, is more invasive and carries the risk of open brain surgery. However, direct cell implantation bypasses the blood-brain barrier and reduces the first-pass effect, effectively increasing the therapeutic cell deposition at its intended site of action. These benefits must be weighed with the risk of graft-versus-host immune response. Rigorous clinical trials are underway to assess the safety and efficacy of intracerebral transplants, and if successful will lead to widely available stem cell therapies for neurologic diseases in the coming years.

Background: Surgery is indicated in cases of mesial temporal lobe epilepsy(MTLE) that are refractory to medical management. The inferior temporal gyrus (ITG) approach provides access to the mesial temporal lobe (MTL) structures with minimal tissue disruption. Reported neuropsychology outcomes following this approach are limited., Objective: To report neuropsychological outcomes using an ITG approach to amygdalohippocampectomy (AH) in patients with medically refractory MTLE based on a prospective design., Methods: Fifty-four participants had Engel class I/II outcome following resection of MTL using the ITG approach. All participants had localization-related epilepsy confirmed by long-term surface video-electroencephalography and completed pre/postsurgical evaluations that included magnetic resonance imaging (MRI), Wada test or functional MRI, and neuropsychology assessment., Results: Clinical semiology/video-electroencephalography indicated that of the 54 patients, 28 (52%) had left MTLE and 26 (48%) had right MTLE. Dominant hemisphere resections were performed on 23 patients (43%), nondominant on 31(57%). Twenty-nine (29) had pathology-confirmed mesial temporal sclerosis (MTS). Group level analyses found declines in verbal memory for patients with language-dominant resections (P < .05). No significant decline in neuropsychological measures occurred for patients with MTS. Participants without MTS who underwent a language-dominant lobe resection exhibited a significant decline in verbal and visual memory (P < .05). Nondominant resection participants did not exhibit significant change in neuropsychology scores (P > .05)., Conclusion: Neuropsychology outcomes of an ITG approach for selective mesial temporal resection are comparable to other selective AH techniques showing minimal adverse cognitive effects. These data lend support to the ITG approach for selective AH as an option for MTLE.

Background: Despite rigorous preoperative evaluation, epilepsy surgery achieves seizure freedom in only two-thirds of cases. Current preoperative evaluation does not include a detailed network analysis despite the association of network-level changes with epilepsy., Objective: We sought to create a software algorithm to map individualized epilepsy networks by combining noninvasive electroencephalography (EEG) source localization and nonconcurrent resting state functional magnetic resonance imaging (rsfMRI)., Methods: Scalp EEG and rsfMRI data were acquired for three sample cases: one healthy control case, one case of right temporal lobe epilepsy, and one case of bitemporal seizure onset. Data from rsfMRI were preprocessed, and a time-series function was extracted. Connection coefficients were used to threshold out spurious connections and model global functional networks in a 3D map. Epileptic discharges were localized using a forward model of cortical mesh dipoles followed by an empirical Bayesian approach of inverse source reconstruction and co-registered with rsfMRI. Co-activating brain regions were mapped., Results: Three illustrative sample cases are presented. In the healthy control case, the software showed symmetrical global connectivity. In the right temporal lobe epilepsy case, asymmetry was found in the global connectivity metrics with a paucity of connectivity ipsilateral to the epileptogenic cortex. The superior longitudinal fasciculus, uncinate fasciculus, and commissural fibers connecting disparate and discontinuous cortical regions involved in the epilepsy network were visualized. In the case with bitemporal lobe epilepsy, global connectivity was symmetric. It showed a network of correlating cortical activity local to epileptogenic tissue in both temporal lobes. The network involved white matter tracks in a similar pattern to those seen in the right temporal case., Conclusions: This modeling algorithm allows better definition of the global brain network and potentially demonstrates differences in connectivity between an epileptic and a non-epileptic brain. This finding may be useful for mapping cortico-cortical connections representing the putative epilepsy networks. With this methodology, we localized the epileptogenic brain and showed network asymmetry and long-distance cortical co-activation. This software tool is the first to use a multimodal, nonconcurrent, and noninvasive approach to model and visualize the epilepsy network., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Patients with epilepsy (PWE) may suffer from comorbid psychogenic nonepileptic seizures (PNES). The efficacy of vagus nerve stimulation (VNS) in the treatment of epilepsy and depression is established, however the impact on PNES is unknown. Since many patients with PNES have comorbid depression, we explored the impact on quality of life (QOL) that VNS has on PWE and PNES., Methods: The video electroencephalogram (vEEG) of all patients who underwent VNS at our institution was reviewed. Patients diagnosed with both psychogenic seizures and epileptic seizures on their vEEG were included in this study. These patients were contacted, and given a QOLIE-31 survey to assess their quality of life after VNS. Patients also completed a separate survey created by our group to categorize the quartile of their improvement. Pre-operative psychiatric disease was retrospectively reviewed., Results: From a period of 2001 to 2016, 518 patients underwent placement of VNS for drug resistant epilepsy (DRE) at our institution. In total, 16 patients were diagnosed with both epilepsy and PNES. 11/16 patients responded to our questionnaire and survey. 9 out of 11 patients felt that their epileptic seizures had improved after VNS, while 7 of the 11 patients felt that their psychogenic episodes had improved. 2(28.6%), 1 (14.3%), and 4 (57.1%) of participants said their PNES improved by 25-50%, 50-75%, and 75-100%, respectively. 3(27.3%), 3 (27.3%), 1 (9.1%), and 4 (36.4%) of the participants said their epileptic seizures improved by 0-25%, 25-50%, 50-75%, and 75-100%, respectively. The average overall score for quality of life for the study participants was found to be 51 (±8) out of 100., Conclusion: Patients with epilepsy and comorbid PNES may benefit from VNS. It is unclear whether the benefit is conferred strictly from decreased epileptic seizure burden. The possible effect on PNES may be related to the known effect of VNS on depression. Further studies are necessary to elucidate the role of VNS in the treatment of PNES and possibly other psychiatric disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Epilepsy is considered a chronic neurological disorder and is accompanied by persistent and diverse disturbances in electrical brain activity. While antiepileptic pharmaceuticals are still the predominant treatment for epilepsy, the advent of numerous surgical interventions has further improved outcomes for patients. Despite these advancements, a subpopulation continues to experience intractable seizures which are resistant to current conventional and nonconventional therapeutic options. In this review, we begin with an introduction to the clinical presentation of epilepsy before discussing the clinically relevant laboratory models of epilepsy. Finally, we explore the implications of regenerative medicine - including cell therapy, neuroprotective agents, and electrical stimulation - for epilepsy, supplemented with our laboratory's data. This paper is a review article. Referred literature in this paper has been listed in the references section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences., Competing Interests: There are no conflicts of interest.

There is a new focus on minimally invasive treatments for medically refractory mesial temporal lobe epilepsy (MTLE). MRI-guided laser interstitial thermal therapy (MRgLITT) is one such minimally invasive procedure, which utilizes MRI guidance and real-time feedback to ablate an epileptogenic focus. A total of 38 patients presenting exclusively with MTLE and no other lesions (including neoplasia), who underwent MRgLITT were reviewed. We evaluated a number of outcome measures, including seizure freedom, neuropsychological performance, complications, and other considerations. Eighteen (53%) had an Engel class I outcome, 10 patients had repeat procedures/operations, and 12 post-procedural complications occurred. Follow-up time ranged from 6 to 38.5months. There was a decreased length of procedure time, hospitalization time, and analgesic requirement when compared to open surgery. In cases of well-localized MTLE this procedure may offer similar (albeit slightly lower) rates of seizure freedom versus traditional surgery. MRgLITT may be an alternative treatment option for high risk surgical patients and, more importantly, could increase referrals for surgery in patients with medically refractory MTLE. However, data is limited and long-term outcomes have not been evaluated. Further investigation is required to understand the potential of this minimally invasive technique for MTLE., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Diffusion tensor imaging (DTI) is a relatively new imaging modality that has found many peri-operative applications in neurosurgery., Methods: A comprehensive survey of the applications of diffusion tensor imaging (DTI) in planning for temporal lobe epilepsy surgery was conducted. The presentation of this literature is supplemented by a case illustration., Results: The authors have found that DTI is well utilized in epilepsy surgery, primarily in the tractography of Meyer's loop. DTI has also been used to demonstrate extratemporal connections that may be responsible for surgical failure as well as perioperative planning. The tractographic anatomy of the temporal lobe is discussed and presented with original DTI pictures., Conclusions: The uses of DTI in epilepsy surgery are varied and rapidly evolving. A discussion of the technology, its limitations, and its applications is well warranted and presented in this article.

The endoplasmic reticulum-lysosome-Golgi network plays an important role in Reelin glycosylation and its proteolytic processing. Golgi complex fragmentation is associated with the separation of Reelin from this network. Kainic acid (KA) is an excitotoxic agent commonly used to induce epilepsy in rodents. The relationship between KA-induced neuronal damage and Golgi complex fragmentation has not been investigated, leaving a major gap in our understanding of the molecular mechanism underlying the development of pathophysiology in epilepsy. We cultured primary rat cortical neurons eitherin ambient condition (control) or treated with a range of KA doses to reveal whether Golgi complex fragmentation impaired neuronal function. The half-life maximal inhibitory concentration (IC50) value of KA was detected to be approximately 5 μM, whereby at these concentrations, KA impaired neuronal viability, which was closely associated with initial Golgi complex fragmentation and subsequent reduction in both the expression and glycosylation patterns of Reelin. These findings implicate that Golgi complex fragmentation and Reelin dysfunction are key contributors to neuronal cell death in the early stage of epilepsy pathophysiology, thereby representing as novel disease biomarkers, as well as potent therapeutic targets for epilepsy.

This study investigated the Word Memory Test (WMT) Free Recall (FR) subtest as a conventional memory measure. Nineteen participants with pharmacoresistant left temporal lobe epilepsy (LTLE) and 16 with right temporal lobe epilepsy (RTLE) completed the WMT, Rey Auditory Verbal Learning Test (RAVLT), and Wechsler Memory Scale-Fourth Edition Logical Memory (LM) subtest during presurgical evaluation. LTLE participants performed significantly worse on FR subtest (p < .05, [Formula: see text]) and RAVLT Trial 7 (p < .01, [Formula: see text]), but not on LM subtest. Age was a significant covariate for FR (p < .01, [Formula: see text]). Logistic regression revealed FR plus age and RAVLT age-adjusted T-scores both yielded 77.1% classification accuracy and respective diagnostic odds ratios of 11.36 and 11.84. Receiver operating characteristic curves to classify seizure laterality found that RAVLT and FR were significant (area under the curve [AUC] = 0.82 and 0.74), whereas LM was nonsignificant (AUC = 0.67). Cut scores and positive/negative predictive values were established for improved clinical classification., (© The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study identifies potential prognostic factors for favorable anterior mesial temporal lobe (AMTL) resection outcomes in patients with medically refractory temporal lobe epilepsy (TLE) with bilateral features on pre-operative examination., Methods: Thirty-one patients demonstrated bilateral features defined as: bilateral independent temporal or bitemporal ictal onsets on surface or intracranial EEG, or bitemporal interictal epileptiform abnormalities on surface EEG with bilateral radiographic mesial temporal sclerosis. Surgical outcomes were classified according to reduction in seizure frequency: I (100% reduction), II (≥75% reduction), III (50-74% reduction), IV (<50% reduction)., Results: Of 31 patients, 14 (45%) improved to class I and 9 (29%) had a class II outcome at an average of 4 years after surgery. Eight (26%) patients did not exhibit good surgical outcome (class III, class IV). We found that neuropsychological and Wada memory scores were significantly correlated (p<0.05) with surgical outcome, and logistic regression found neuropsychological evaluation significantly predicted better surgical outcome (p<0.05)., Conclusions: When bilateral features are present on pre-operative evaluation, neuropsychological and Wada test results can provide unique data to better identify those patients more likely to achieve substantial seizure reduction., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: Cerebral cavernous malformations (CCM) of the temporal lobe often present with seizures. Surgical resection of these lesions can offer durable seizure control. There is, however, no universally accepted methodology for assessing and surgically treating these patients. We propose an algorithm to maximize positive surgical outcomes (seizure control) while minimizing post-surgical neurological deficit., Methods: A retrospective review of 34 patients who underwent epilepsy surgery for radiographically proven temporal lobe CCM was conducted. Patients underwent a relatively standard work-up for seizure localization. In patients with mesial temporal lobe epilepsy (MTLE), a complete resection of the epileptogenic zone was performed including amygdalo-hippocampectomy in addition to a lesionectomy if not contraindicated by pre-operative work-up. Patients with neocortical epilepsy underwent intraoperative electrocorticography (ECoG)-guided lesionectomy., Results: Seizure-free rate for mesial and neocortical (anterior, lateral, and basal) location was 90 vs. 83 %, respectively. Complete resection of the lesion, irrespective of location, was statistically significant for seizure control (p = 0.018). There was no difference in seizure control based on disease duration or location (p > 0.05). Patients with mesial temporal CCM who presented with MTLE were presumed to also have mesial temporal sclerosis (MTS), or dual pathology. These patients underwent routine resection of the mesial structures. Interestingly, patients who had MTLE and basal (neocortical) lesions who underwent a mesial resection for suspected MTS were found not to have dual pathology., Conclusions: Patients with temporal lobe CCM should be offered resection for durable seizure control, prevention of secondary epileptogenic foci, and elimination of hemorrhage risk. The preoperative work-up should follow a team approach. Surgical intervention should include complete lesionectomy in all cases. Intra or extra-operative ECoG for neocortical lesions may be beneficial. Management of mesial temporal CCMs (archicortex) should consider resection of a well-defined epileptogenic zone (including mesial structures) due to high probability of pathologically proven MTS. The use of this treatment algorithm is useful for the education and treatment of these patients.

Selective anterior mesial temporal lobe (AMTL) resection is considered a safe and effective treatment for medically refractory mesial temporal lobe epilepsy (MTLE). However, as with any open surgical procedure, older patients (aged 50+) face greater risks. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has shown recent potential as an alternative treatment for MTLE. As a less invasive procedure, MRgLITT could be particularly beneficial to older patients. To our knowledge, no study has evaluated the safety and efficacy of MRgLITT in this population. Seven consecutive patients (aged 50+) undergoing MRgLITT for MTLE were followed prospectively to assess surgical time, complications, postoperative pain control, length of stay (LOS), operating room (OR) charges, total hospitalization charges, and seizure outcome. Five of these patients were assessed at the 1-year follow-up for seizure outcome. These data were compared with data taken from 7 consecutive patients (aged 50+) undergoing AMTL resection. Both groups were of comparable age (mean: 60.7 (MRgLITT) vs. 53 (AMTL)). One AMTL resection patient had a complication of aseptic meningitis. One MRgLITT patient experienced an early postoperative seizure, and two MRgLITT patients had a partial visual field deficit. Seizure-freedom rates were comparable (80% (MRgLITT) and 100% (AMTL) (p>0.05)) beyond 1year postsurgery (mean follow-up: 1.0years (MRgLITT) vs. 1.8years (AMTL)). Mean LOS was shorter in the MRgLITT group (1.3days vs. 2.6days (p<0.05)). Neuropsychological outcomes were comparable. Short-term follow-up suggests that MRgLITT is safe and provides outcomes comparable to AMTL resection in this population. It also decreases pain medication requirement and reduces LOS. Further studies are necessary to assess the long-term efficacy of the procedure., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To assess the use of subdural intracranial EEG (iEEG) on postoperative outcomes at an epilepsy center., Methods: Ninety-one epilepsy patients underwent iEEG. Array design was compared with noninvasive EEG with over 1 year of outcome. Patient demographics, implanted brain sites, electrodes, contacts/site, and surgical location were correlated with outcome. Fisher exact test and logistics regression were used to evaluate significance (P ≤ 0.05)., Results: Of ninety-one women, 55 (mean age, 32.3 years; range, 11-60) underwent tailored iEEG. Seventy of ninety-one (76.9%) resections (70% temporal) yielded 24/91 (26.4%) seizure free (SF). Strips (57.1%), grids (5.5%), or both (37.4%) for iEEG use was commonly bilateral (58.2%; 65.3% bitemporal) but did not predict outcome (P = NS). A lesion (28/91) did predict a SF outcome (42.9%). The iEEG localized 45.7% of seizures beyond scalp EEG and changed the localization or lateralization in 75.7% of resected patients. Electrode design, localization, lateralization, and site of resection did not correlate with outcome (P = NS). Overall, iEEG use portended a non-SF outcome (P ≤ 0.0001)., Conclusions: The use of iEEG selected 46% additional patients for surgery, yet only 26% became SF. A magnetic resonance imaging lesion predicted a SF or seizure-improved outcome. Although iEEG changed the localization and lateralization of scalp ictal EEG in three quarters of patients, its use was a negative predictor for a favorable outcome. Preoperative counseling should emphasize expectations for seizure reduction in patients requiring iEEG.

When differences exist, women tend to outperform men on measures of verbal fluency, possibly due to greater bilateral language representation. Patients with temporal lobe epilepsy (TLE) have a higher rate of atypical cortical language representation than the general population, making them a population of interest for the study of language. For the current study, 78 TLE patients (51% male, 51% left temporal focus) underwent pre-surgical neuropsychological evaluations. Retrospective data analyses investigated the impact of seizure laterality and sex on letter and semantic verbal fluency. Results indicated an interaction between sex and laterality for semantic, but not letter, verbal fluency. Males with left TLE exhibited significantly worse semantic fluency than males with right TLE, whereas females' semantic fluency did not differ by seizure focus. These data indicate that females with TLE may indeed engage in more bilateral hemispheric processing of semantic verbal fluency, whereas males may be more reliant on left temporal cortical function for this task., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This study evaluated the accuracy of the Wechsler Memory Scale--Fourth Edition (WMS-IV) in identifying functional cognitive deficits associated with seizure laterality in localization-related temporal lobe epilepsy (TLE) relative to a previously established measure, the Rey Auditory Verbal Learning Test (RAVLT). Emerging WMS-IV studies have highlighted psychometric improvements that may enhance its ability to identify lateralized memory deficits. Data from 57 patients with video-EEG-confirmed unilateral TLE who were administered the WMS-IV and RAVLT as part of a comprehensive presurgical neuropsychological evaluation for temporal resection were retrospectively reviewed. We examined the predictive accuracy of the WMS-IV not only in terms of verbal versus visual composite scores but also using individual subtests. A series of hierarchal logistic regression models were developed, including the RAVLT, WMS-IV delayed subtests (Logical Memory, Verbal Paired Associates, Designs, Visual Reproduction), and a WMS-IV verbal-visual memory difference score. Analyses showed that the RAVLT significantly predicted laterality with overall classification rates of 69.6% to 70.2%, whereas neither the individual WMS-IV subtests nor the verbal-visual memory difference score accounted for additional significant variance. Similar to previous versions of the WMS, findings cast doubt as to whether the WMS-IV offers significant incremental validity in discriminating seizure laterality in TLE beyond what can be obtained from the RAVLT., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Study Design: Retrospective review/case series., Objective: This study aims to present the clinical feasibility of condylar fixation in occipitocervical (OC) fusion. Here, we present the largest clinical series to date of patients who underwent OC fusion via cervicocondylar fixation using a polyaxial screw/rod construct., Summary of Background Data: The novel technique using the occipital condyles as the sole cranial fixation point has been described. Both cadaveric and biomechanical studies, in recent literature, have shown technical feasibility and surgical safety of condylar fixation., Methods: We retrospectively reviewed a prospectively acquired database of all patients treated with OC fusion via cervicocondylar fixation at our institution between 2007 and 2011. All patients were scheduled for follow-up postoperatively at weeks 2, 6, 12, 24, and annually thereafter. Outcome measures included estimated blood loss, operative time, complications, integrity of the construct, and fusion rates. Exclusion criteria included condylar fracture, previous cervical fusion, or vertebral artery injury. Enrolled patients subsequently underwent posterior OC fixation using occipital condyle, C1 lateral mass, and/or C2 pars interarticularis screw fixation. Subaxial cervical fixation consisted of lateral mass screw placement. Intraoperative fluoroscopy and hypoglossal monitoring were used., Results: We identified 12 consecutive patients who underwent OC fusion using the occipital condyle as the cranial fixation point using polyaxial screws. The mean operative time was 283 minutes (192-416). The mean total blood loss was 229 mL (100-400). Mean follow-up was 21.4 months (4-39). One patient suffered from a superficial wound infection. There were no neural or vascular complications. Radiographic evidence of OC fusion was noted for all patients with >6-month follow-up., Conclusions: OC fusion using occipital condylar screws is a feasible alternative to current occipital plate fixation. Condylar screw fixation can be performed safely with successful arthrodesis as a treatment for OC instability in patients.