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Jerry J Shih,1 William O Tatum,1 Leslie A Rudzinski21Department of Neurology, Mayo Clinic, Jacksonville, FL, USA; 2Department of Neurology, Emory University, Atlanta, GA, USAAbstract: Perampanel (2-[2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl] benzonitrile hydrate) is the latest in the line of new antiepileptic drugs with a novel mechanism of action. Perampanel inhibits α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-induced increases in intracellular Ca2+ and selectively blocks AMPA receptor-mediated synaptic transmission, thus reducing neuronal excitation. Three Phase III multicenter, randomized, double-blind, placebo-controlled trials demonstrated the efficacy and good tolerability of perampanel as adjunctive treatment in patients with refractory partial-onset seizures. The drug is approved for use in the European Union and United States, with expected release onto the American market in June–September 2013, pending US Drug Enforcement Agency classification. The pharmacology of perampanel offers potential as more than just another new antiepileptic drug. This first-in-class drug will provide another option for practitioners of rational polytherapy. As an AMPA-receptor antagonist, perampanel may possess antiepileptogenic properties in addition to its demonstrated antiseizure properties.Keywords: perampanel, mechanism of action, efficacy, review

Long-term electroencephalographic monitoring (LTM) is the capability of recording the EEG over long periods of time and not a specific duration. Prolonged EEG recording is used primarily for epilepsy monitoring, but LTM is also used in the intensive care unit, the operating room, and the emergency department. The purpose of LTM is to expand the limited time sampling associated with shorter 'routine' EEG recording. Audiovisual monitoring may also be used in conjunction with LTM to evaluate simultaneously a specific clinical behavior that may or may not be associated with EEG alteration. This is typically performed in a hospital setting for safety and ancillary testing purposes. LTM is used most frequently in the diagnosis and management of seizures and 'spells,' but has also gained wider application in the evaluation of sleep disorders, cerebrovascular disease, psychiatric conditions, and movement disorders. Computer-assisted LTM systems that process, analyze, compress and store data digitally have become widely available in clinical practice both in the hospital as well as outside the hospital when the patient is ambulatory. [ABSTRACT FROM AUTHOR]

Significant advances have been made in the diagnosis and treatment of epilepsy over the past decade. With the advent of electroencephalographic video monitoring, physicians are now able to reliably differentiate epilepsy from other conditions that can mimic it, such as pseudoseizures. In addition, neuroimaging has changed the way treatment for difficult epilepsy is approached. As a result, the classification systems that have been in use since the early 1980s are currently being revised. A broader range of treatment options for epilepsy is now available. Many new antiepileptic drugs have become available in recent years, including felbamate, gabapentin, lamotrigine, topiramate, tiagabine, levetiracetam, oxcarbazepine and zonisamide. These medications offer options for patients with epilepsy whose seizures cannot be controlled using the classic agents. Several classic antiepileptic drugs have been modified and reformulated. The ketogenic diet has resurfaced as a treatment option in certain types of epilepsy. The vagus nerve stimulator, approved in 1997, represents a completely new treatment modality for patients with seizures not controlled by medications. Epilepsy surgery is now a well-documented and effective treatment for some patients with intractable epilepsy. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy is a common form of epilepsy that is often associated with hippocampal sclerosis (HS). Although HS is commonly considered a binary assessment in radiologic evaluation, it is known that histopathologic changes occur in distinct clusters. Some subtypes of HS only affect certain subfields, resulting in minimal changes to the overall volume of the hippocampus. This is likely a major reason why whole hippocampal volumetrics have underperformed versus expert readers in the diagnosis of HS. With recent advancements in MRI technology, it is now possible to characterize the substructure of the hippocampus more accurately. However, this is not consistently addressed in radiographic evaluations. The histologic subtype of HS is critical for prognosis and treatment decision-making, necessitating improved radiologic classification of HS. The International League Against Epilepsy (ILAE) has issued a consensus classification scheme for subtyping HS histopathologic changes. This review aims to explore how the ILAE subtypes of HS correlate with radiographic findings, introduce a grading system that integrates radiologic and pathologic reporting in HS, and outline an approach to detecting HS subtypes by using MRI. This framework will not only benefit current clinical evaluations, but also enhance future studies involving high-resolution MRI in temporal lobe epilepsy., (© 2024 by American Journal of Neuroradiology.)

Objective: Neuromodulation is a viable option for patients with drug-resistant epilepsies. We reviewed the management of patients with two deep brain neurostimulators. In addition, patients implanted with a device targeting the centromedian-parafascicular (CM-Pf) nuclear complex supplements this report to provide an illustrative case to implantation and programming a patient with three active devices., Methods: A narrative review using PubMed and Embase identified patients with drug-resistant epilepsy implanted with more than one neurostimulator was performed. Combinations of vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS) were identified. We provide a background of a newly reported case of an adult with a triple implant eventually responding to CM-Pf DBS as the third implant following suboptimal benefit from VNS and RNS., Results: In review of the literature, dual-device therapy is increasing in reports of use with combinations of VNS, RNS, and DBS to treat patients with drug-resistant epilepsy. We review dual-device implants with thalamic DBS device combinations, functional neural networks, and programming patients with dual devices. CM-Pf is a new target for DBS and has shown a variable response in focal epilepsy. We report the unique case of 28-year-old male with drug-resistant focal epilepsy who experienced a 75% seizure reduction with CM-Pf DBS as his third device after suboptimal responses to VNS and RNS. After 9 months, he also experienced seizure freedom from recurrent focal to bilateral tonic-clonic seizures. No medical or surgical complications or safety issues were encountered., Conclusion: We demonstrate safety and feasibility in an adult combining active VNS, RNS, and CM-Pf DBS. Patients with dual-device therapy who experience a suboptimal response to initial device use at optimized settings should not be considered a neuromodulation "failure." Strategies to combine devices require a working knowledge of brain networks., (© 2024 International League Against Epilepsy.)

In the case of suspicion of nonconvulsive status epilepticus (NCSE), reactivity on electroencephalograms (EEGs) can provide valuable diagnostic information. Reactivity refers to responses to auditory or somatosensory stimulation, with changes in amplitude and frequency of background activity. Because of self-perpetuating processes and the failure of self-terminating mechanisms, status epilepticus is unlikely to cease when patients spontaneously move, and it cannot typically be stopped by external stimulation (i.e., auditory and tactile stimuli). The defining EEG characteristic of absence status epilepticus is the presence of bilateral, synchronous, symmetric, rhythmic paroxysmal activity that shows little or no reactivity to sensory stimulation. On the other hand, in metabolic/toxic or multifactorial encephalopathies, triphasic waves (TWs) are influenced by the level of vigilance. TWs may be transiently abolished when patients increase their level of alertness from a drowsy/lethargic state to a state of wakefulness. This reactivity is only observed when patients can be aroused by a somatosensory or auditory stimulus. This reactivity tends to disappear with increasing severity of the disease and in comatose patients. In patients without preexisting developmental and epileptic encephalopathy, this pattern of stimulus-induced wakefulness with transient improvement of the EEG is a major criterion in determining that the EEG patterns are not ictal. This criterion of reactivity on EEGs, beyond the classical clinical/EEG criteria of NCSE (Salzburg criteria), should now be systematically added., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Normal EEG variants, especially the epileptiform variants, can be challenging to interpret because they often have sharp contours and may be confused with "epileptic" interictal activities. However, they can be recognized by the fact that "most spikes or sharp wave discharges of clinical import are followed by a slow wave or a series of slow deflections" (Maulsby, 1971). If there is no wave after the spike, electroencephalographers should be suspicious of artifacts and normal EEG variants. Most normal EEG variants display a single rhythm with the same frequency within the pattern and the morphology remains stable throughout the entire EEG recording with repetition of the same pattern. In case of doubt or difficulties with a standard EEG, it is recommended to undergo an EEG that includes sleep stages with or without sleep deprivation. Finally, epileptiform is an ambiguous term corresponding to an electroencephalographic trait. Epileptiform does not imply a pathological condition, including epilepsy. The clinical context remains the most paramount in the diagnosis of epilepsy. In this article, we propose a set of rules and guidelines to identify normal EEG variants in EEG tracings and normal variation of the background activity. It is not easy to accurately assign a specific/precise name to all EEG activity, but with an orderly approach to EEG that involves using a set of criteria, nonepileptic activity can be identified., (© 2024. The Author(s).)

While abnormalities of the hippocampus have been well characterized in temporal lobe epilepsy, various additional temporal lobe abnormalities have also been described. One poorly understood entity, the so-called temporal pole blurring (TPB), is one of the more frequently described neocortical abnormalities in TLE and is thought to represent dysmyelination and axonal loss due to chronic electrical perturbations in early age-onset temporal lobe epilepsy. In this study, we describe the first reported cases of TPB diagnosed by a recently described MRI sequence known as 3D Edge-Enhancing Gradient Echo (3D-EDGE), which has an effective "myelin weighting" making it exquisitely sensitive to this temporal pole dysmyelination. The value of detection of TPB lies in lateralizing seizure onset, as well as predicting a lower baseline neuropsychological performance compared to temporal lobe epilepsy without TPB. Additionally, it is critical to not mistake TPB for alternative diagnoses, such as focal cortical dysplasia or neoplasm., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Tumor-related epilepsy (TRE) is a frequent and major consequence of brain tumors. Management of TRE is required throughout the course of disease and a deep understanding of diagnosis and treatment is key to improving quality of life. Gross total resection is favored from both an oncologic and epilepsy perspective. Shared mechanisms of tumor growth and epilepsy exist, and emerging data will provide better targeted therapy options. Initial treatment with antiseizure medications (ASM) in conjunction with surgery and/or chemoradiotherapy is typical. The first choice of ASM is critical to optimize seizure control and tolerability considering the effects of the tumor itself. These agents carry a potential for drug-drug interactions and therefore knowledge of mechanisms of action and interactions is needed. A review of adverse effects is necessary to guide ASM adjustments and decision-making. This review highlights the essential aspects of diagnosis and treatment of TRE with ASMs, surgery, chemotherapy, and radiotherapy while indicating areas of uncertainty. Future studies should consider the use of a standardized method of seizure tracking and incorporating seizure outcomes as a primary endpoint of tumor treatment trials., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Awake craniotomy with electrocorticography (ECoG) and direct electrical stimulation (DES) facilitates lesionectomy while avoiding adverse effects. Early postoperative seizures (EPS), occurring within 7 days following surgery, can lead to morbidity. However, risk factors for EPS after awake craniotomy including clinical and ECoG data are not well defined., Methods: We retrospectively studied the incidence and risk factors of EPS following awake craniotomy for lesionectomy, and report short-term outcomes between January 1, 2020, and December 31, 2022., Results: We included 138 patients (56 female) who underwent 142 awake craniotomies, average age was 50.78 ± 15.97 years. Eighty-eight (63.7%) patients had a preoperative history of tumor-related epilepsy treated with antiseizure medication (ASM), 12 (13.6%) with drug-resistance. All others (36.3%) received ASM prophylaxis with levetiracetam perioperatively and continued for 14 days. An equal number of cases (71) each utilized a novel circle grid or strip electrodes for ECoG. There were 31 (21.8%) cases of intraoperative seizures, 16 with EPS (11.3%). Acute abnormality on early postoperative neuroimaging (P = 0.01), subarachnoid hemorrhage (P = 0.01), young age (P = 0.01), and persistent postoperative neurologic deficits (P = 0.013) were associated with EPS. Acute abnormality on neuroimaging remained significant in multivariate analysis. Outcomes during hospitalization and early outpatient follow up were worse with EPS., Conclusions: We report novel findings using ECoG and clinical features to predict EPS, including acute perioperative brain injury, persistent postoperative deficits and young age. Given worse outcomes with EPS, clinical indicators for EPS should alert clinicians of potential need for early postoperative EEG monitoring and perioperative ASM adjustment., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Purpose: Cerebral amyloid angiopathy (CAA) is a common cause of intracranial hemorrhage (ICH), which is a risk factor for seizures. The incidence and risk factors of seizures associated with a heterogeneous cohort of CAA patients have not been studied., Methods: We conducted a retrospective study of patients with CAA treated at Mayo Clinic Florida between 1 January 2015 and 1 January 2021. CAA was defined using the modified Boston criteria version 2.0. We analyzed electrophysiological and clinical features, and comorbidities including lobar ICH, nontraumatic cortical/convexity subarachnoid hemorrhage (cSAH), superficial siderosis, and inflammation (CAA with inflammation [CAA-ri]). Cognition and mortality were secondary outcomes. Univariate and multivariate analyses were performed to determine risk of seizures relative to clinical presentation., Results: Two hundred eighty-four patients with CAA were identified, with median follow-up of 35.7 months (interquartile range = 13.5-61.3 months). Fifty-six patients (19.7%) had seizures; in 21 (37.5%) patients, seizures were the index feature leading to CAA diagnosis. Seizures were more frequent in females (p = 0.032) and patients with lobar ICH (p = 0.002), cSAH (p = 0.030), superficial siderosis (p < 0.001), and CAA-ri (p = 0.005), and less common in patients with microhemorrhage (p = 0.006). After controlling for age and sex, lobar ICH (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.1-4.2), CAA-ri (OR = 3.8, 95% CI = 1.4-10.3), and superficial siderosis (OR = 3.7, 95% CI = 1.9-7.0) were independently associated with higher odds of incident seizures., Conclusions: Seizures are common in patients with CAA and are independently associated with lobar ICH, CAA-ri, and superficial siderosis. Our results may be applied to optimize clinical monitoring and management for patients with CAA., (© 2023 European Academy of Neurology.)

Background and Objectives: Smartphones are a ubiquitous part of society with increasing use as a healthcare tool. We aimed to analyze the published literature on smartphone usage within the field of Neurology to define the scientific landscape and forecast future research initiatives., Methods: We performed a bibliometric review of smartphone uses in Neurology based on a search of two Web of Science databases from inception through September 16, 2022. This librarian-guided review was conducted using Bibliometrix for data assessment and visualization. Temporal trends in publications, citation counts, collaborations, and author affiliations were among key metrics evaluated. VOS viewer identified hot spots based on generating co-occurrences and bibliographic coupling mapping., Results: Our search found 3,920 publications. The U.S. produced the most topic-based publications, collaborating most frequently with U.K., Canada, and China-based authors. The most prolific institutions included Karolinska Institute, University of Sydney, and University of Pittsburgh. Bioelectromagnetics , Stroke , and Neurology were the most cited journals. Rapid growth in scientific production occurred in recent years, including during the COVID-19 pandemic. Hotspots and keyword co-occurrence included telehealth, machine learning, and self-management. Temporal trends reflect transitioning from a focus of initial publications regarding mobile phone safety to more recent application of smartphones as "smart" tools for single modality diagnosis, monitoring, management, and treatment of neurological diseases., Discussion: There has been rapid expansion of the published literature on smartphone uses in Neurology. Initial focus on smartphones and health risk has shifted to uses for neurological disease diagnosis, detection, and management, with relevance as a global interface for collaboration and clinical practice., 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 © 2023 Tatum, Acton, Freund, de la Cruz Gutierrez, Feyissa and Brigham.)

Intraoperative electrocorticography (iECoG) is used as an adjunct to localize the epileptogenic zone during surgical resection of brain tumors in patients with focal epilepsies. It also enables monitoring of after-discharges and seizures with EEG during functional brain mapping with electrical stimulation. When seizures or after-discharges are present, they complicate accurate interpretation of the mapping strategy to outline the brain's eloquent function and can affect the surgical procedure. Recurrent seizures during surgery requires urgent treatment and, when occurring during awake craniotomy, often leads to premature termination of brain mapping due to post-ictal confusion or sedation from acute rescue therapy. There are mixed results in studies on efficacy with iECoG in patients with epilepsy and brain tumors influencing survival and functional outcomes following surgery. Commercially available electrode arrays have inherent limitations. These could be improved with customization potentially leading to greater precision in safe and maximal resection of brain tumors. Few studies have assessed customized electrode grid designs as an alternative to commercially available products. Higher density electrode grids with intercontact distances less than 1 cm improve spatial delineation of electrophysiologic sources, including epileptiform activity, electrographic seizures, and afterdischarges on iECoG during functional brain mapping. In response to the shortcomings of current iECoG grid technologies, we designed and developed a novel higher-density hollow circular electrode grid array. The 360-degree iECoG monitoring capability allows continuous EEG recording during surgical intervention through the aperture with and without electrical stimulation mapping. Compared with linear strip electrodes that are commonly used for iECoG during surgery, the circular grid demonstrates significant benefits in brain tumor surgery. This includes quicker recovery of post-operative motor deficits (2.4 days versus 9 days, p = 0.05), more extensive tumor resection (92.0% versus 77.6%, p = 0.003), lesser reduction in Karnofsky Performance scale postoperatively (-2 versus -11.6, p = 0.007), and more sensitivity to recording afterdischarges. In this narrative review, we discuss the advantages and disadvantages of commercially available recording devices in the operating room and focus on the usefulness of the higher-density circular grid., (© 2023 IOP Publishing Ltd.)

Purpose: Awake craniotomy with intraoperative functional brain mapping (FBM) bedside neurological testing is an important technique used to optimize resective brain surgeries near eloquent cortex. Awake craniotomy performed with electrocorticography (ECoG) and direct electrical stimulation (DES) for FBM can delineate eloquent cortex from lesions and epileptogenic regions. However, current electrode technology demonstrates spatial limitations. Our group has developed a novel circular grid with the goal of improving spatial recording of ECoG to enhance detection of ictal and interictal activity., Methods: This retrospective study was approved by the institutional review board at Mayo Clinic Florida. We analyzed patients undergoing awake craniotomy with ECoG and DES and compared ECoG data obtained using the 22 contact circular grid to standard 6 contact strip electrode., Results: We included 144 cases of awake craniotomy with ECoG, 73 using circular grid and 71 with strip electrode. No significant differences were seen regarding preoperative clinical and demographic data, duration of ECoG recording (p = 0.676) and use of DES (p = 0.926). Circular grid was more sensitive in detecting periodic focal epileptiform discharges (PFEDs) (p = 0.004), PFEDs plus (p = 0.032), afterdischarges (ADs) per case (p = 0.022) at lower minimum (p = 0.012) and maximum (p < 0.0012) intensity stimulation, and seizures (p = 0.048). PFEDs (p < 0.001), PFEDs plus (p < 0.001), and HFOs (p < 0.001) but not ADs (p = 0.255) predicted electrographic seizures., Conclusion: We demonstrate higher sensitivity in detecting ictal and interictal activity on ECoG during awake craniotomy with a novel circular grid compared to strip electrode, likely due to better spatial sampling during ECoG. We also found association between PFEDs and intraoperative seizures., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To identify risk factors for developing glioblastoma (GBM) related preoperative (PRS) and postoperative seizures (POS). Also, we aimed to analyze the impact of PRS and POS on survival in a GBM cohort according to the revised 2021 WHO glioma classification., Methods: We performed a single-center retrospective cohort study of patients with GBM (according to the 2021 World Health Organization Classification) treated at Mayo Clinic Florida between January 2018 and July 2022. Seizures were stratified into preoperative seizures (PRS) and postoperative seizures (POS, >7 days after surgery). Associations between patients' characteristics and overall survival with PRS and POS were assessed., Results: One hundred nineteen adults (mean =60.9 years), 49 (41.2 %) females, were identified. The rates of PRS and POS in the cohort were 35.3 % (n = 42) and 37.8 % (n = 45), respectively. Patients with PRS were younger (p = 0.035) and were likely to undergo intraoperative electrocorticography. The incidence of PRS (p = 0.049) and POS (p<0.001) was lower among patients with tumors located in the occipital location. PRS increased the risk of POS after adjusting for age and sex (RR: 2.59, CI = 1.44-4.65, p = 0.001). There was no association between PRS or POS and other patient-related factors, including several tumor molecular markers (TMMs) examined. PRS (p = 0.036), POS (p<0.001), and O6-Methylguanine-DNA Methyltransferase (MGMT) promotor methylation status (p = 0.032) were associated with longer survival time., Conclusions: PRS and POS are associated with non-occipital tumor location and longer survival time in patients with GBM. While younger ages predicted PRS, PRS predicted POS. Well-designed prospective studies with larger sample sizes are needed to clarify the influence of TMMs in the genesis of epileptic seizures in patients with GBM., Competing Interests: Declaration of Competing Interest Drs. Feyissa, Sanchez-Boluarte, Moniz-Garcia, Chaichana, Sherman, Freund, Middlebrooks, Tatum, Sirven, and Quinones-Hinojosa report no disclosures relevant to the manuscript., (Copyright © 2023. Published by Elsevier Ltd.)

Background and Objectives: We recently published expert consensus-based curricular objectives for routine EEG (rEEG) interpretation for adult and child neurology residents. In this study, we used this curriculum framework to develop and validate an online, competency-based, formative and summative rEEG examination for neurology residents., Methods: We developed an online rEEG examination consisting of a brief survey and 30 multiple-choice questions covering EEG learning objectives for neurology residents in 4 domains: normal, abnormal, normal variants, and artifacts. Each question contained a deidentified EEG image, displayed in 2 montages (bipolar and average), reviewed and optimized by the authors to address the learning objectives. Respondents reported their level of confidence (LOC, 5-point Likert scale) with identifying 4 categories of EEG findings independently: states of wakefulness/sleep, sleep structures, normal variants, and artifacts. Accuracy and item discrimination were calculated for each question and LOC for each category. The test was disseminated by the International League Against Epilepsy and shared on social media., Results: Of 2,080 responses, 922 were complete. Respondents comprised clinical neurophysiologists/experts (n = 41), EEG/epilepsy clinical fellows (n = 211), EEG technologists (n = 128), attending neurologists (n = 111), adult neurology residents (n = 227), child neurology residents (n = 108), medical students (n = 24), attending non-neurologists (n = 18), and others (n = 54). Mean overall scores (95% CI) were 82% (77-86) (clinical neurophysiologists), 81% (79-83) (clinical fellows), and 72% (70-73) (adult and child neurology residents). Experts were more confident than clinical fellows in all categories but sleep structures. Experts and clinical fellows were more confident than residents in all 4 categories. Among residents, accuracy and LOC increased as a function of prior EEG weeks of training. Accuracy improved from 67% (baseline/no prior EEG training) to 77% (>12 prior EEG weeks). More than 8 weeks of EEG training was needed to reach accuracy comparable with clinical neurophysiologists on this rEEG examination. Increase in LOC was slower and less robust than increase in accuracy. All but 3 questions had a high discrimination index (>0.25)., Discussion: This online, competency-based rEEG examination, mapped to a published EEG curriculum, has excellent psychometrics and differentiates experienced EEG readers from adult and child neurology residents. This online tool has the potential to improve resident EEG education worldwide., Competing Interests: F. Nascimento, H. Gao, R. Katyal, R. Matthews, S. Yap, S. Rampp, W. Tatum, S. Beniczky report no disclosures relevant to the manuscript. R.E. Strowd is the Editor-in-Chief of Neurology® Education. Go to Neurology.org/NE for full disclosures., (© 2023 American Academy of Neurology.)

Epilepsy is a common neurological disorder in the United States, affecting approximately 1.2% of the population. Some people with epilepsy may experience seizure clusters, which are acute repetitive seizures that differ from the person's usual seizure pattern. Seizure clusters are unpredictable, are emotionally burdensome to patients and caregivers (including care partners), and require prompt treatment to prevent progression to serious outcomes, including status epilepticus and associated morbidity (e.g., lacerations, fractures due to falls) and mortality. Rescue medications for community use can be administered to terminate a seizure cluster, and benzodiazepines are the cornerstone of rescue treatment. Despite the effectiveness of benzodiazepines and the importance of a rapid treatment approach, as many as 80% of adult patients do not use rescue medication to treat seizure clusters. This narrative review provides an update on rescue medications used for treatment of seizure clusters, with an emphasis on clinical development and study programs for diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray. Results from long-term clinical trials have shown that treatments for seizure clusters are effective. Intranasal benzodiazepines provide ease of use and patient and caregiver satisfaction in pediatric and adult patients. Adverse events attributed to acute rescue treatments have been characterized as mild to moderate, and no reports of respiratory depression have been attributed to treatment in long-term safety studies. The implementation of an acute seizure action plan to facilitate optimal use of rescue medications provides an opportunity for improved management of seizure clusters, allowing those affected to resume normal daily activities more quickly., (© 2023. The Author(s).)

Background and Objectives: To evaluate the use of transparent goggles in the prevention of eye closure and subsequent seizures due to fixation-off sensitivity (FOS)., Methods: An N-of-1 trial was conducted during which 7 consecutive cycles of showering with and without goggles were evaluated., Results: We found 100% provocation of eyelid myoclonia during each cycle without goggle usage on daily review of smartphone videos with seizure freedom during each cycle with goggles. The semiology on smartphone videos was identical to absences with eyelid myoclonia confirmed by inpatient video-EEG monitoring. At the 6-month follow-up, subjective quality of life improved with no shower-related seizures, greater independence while bathing, and reduction of anticipatory anxiety., Discussion: Transparent swimming goggles were effective in this N-of-1 trial to render a patient with drug-resistant epilepsy seizure-free and avert ongoing injury due to FOS. Behavioral modification is a critical adjunct to medical therapy in patients with fixation-off sensitivity., Competing Interests: The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2023 American Academy of Neurology.)

Historically, periodic EEG patterns were described as any pattern with stereotyped paroxysmal complexes occurring at regular intervals, i.e., the period (T). T is the sum of the duration of the waveform (t1) and, eventually, the duration of the interval between two consecutive waves (t2). The American Clinical Neurophysiology Society introduced the concept of a clearly discernible inter-discharge interval between consecutive waveforms (i.e., t2). As this definition was not applied to what have previously been termed triphasic waves and in some cases of lateralized periodic discharges, we propose reconsideration of terminology that includes historical use of definitions. This will allow the development and usage of the concept for periodic EEG patterns as any runs of stereotyped paroxysmal waveforms separated by nearly identical intervals and prolonged repetitive complexes on the EEG. Prolonged expression means EEG is recorded for a sufficient period of time to prove that the pattern is repetitive, thus resulting in a monomorphic/monotonous pattern. More important than the inter-discharge interval (t2), periodic EEG patterns occur at time regular intervals (T). As a result, periodic EEG activity should be considered along a continuum and not the opposite of rhythmic EEG activity where no interval activity exists between consecutive waveforms., (© 2023. The Author(s).)

Importance: Electroencephalograms (EEGs) are a fundamental evaluation in neurology but require special expertise unavailable in many regions of the world. Artificial intelligence (AI) has a potential for addressing these unmet needs. Previous AI models address only limited aspects of EEG interpretation such as distinguishing abnormal from normal or identifying epileptiform activity. A comprehensive, fully automated interpretation of routine EEG based on AI suitable for clinical practice is needed., Objective: To develop and validate an AI model (Standardized Computer-based Organized Reporting of EEG-Artificial Intelligence [SCORE-AI]) with the ability to distinguish abnormal from normal EEG recordings and to classify abnormal EEG recordings into categories relevant for clinical decision-making: epileptiform-focal, epileptiform-generalized, nonepileptiform-focal, and nonepileptiform-diffuse., Design, Setting, and Participants: In this multicenter diagnostic accuracy study, a convolutional neural network model, SCORE-AI, was developed and validated using EEGs recorded between 2014 and 2020. Data were analyzed from January 17, 2022, until November 14, 2022. A total of 30 493 recordings of patients referred for EEG were included into the development data set annotated by 17 experts. Patients aged more than 3 months and not critically ill were eligible. The SCORE-AI was validated using 3 independent test data sets: a multicenter data set of 100 representative EEGs evaluated by 11 experts, a single-center data set of 9785 EEGs evaluated by 14 experts, and for benchmarking with previously published AI models, a data set of 60 EEGs with external reference standard. No patients who met eligibility criteria were excluded., Main Outcomes and Measures: Diagnostic accuracy, sensitivity, and specificity compared with the experts and the external reference standard of patients' habitual clinical episodes obtained during video-EEG recording., Results: The characteristics of the EEG data sets include development data set (N = 30 493; 14 980 men; median age, 25.3 years [95% CI, 1.3-76.2 years]), multicenter test data set (N = 100; 61 men, median age, 25.8 years [95% CI, 4.1-85.5 years]), single-center test data set (N = 9785; 5168 men; median age, 35.4 years [95% CI, 0.6-87.4 years]), and test data set with external reference standard (N = 60; 27 men; median age, 36 years [95% CI, 3-75 years]). The SCORE-AI achieved high accuracy, with an area under the receiver operating characteristic curve between 0.89 and 0.96 for the different categories of EEG abnormalities, and performance similar to human experts. Benchmarking against 3 previously published AI models was limited to comparing detection of epileptiform abnormalities. The accuracy of SCORE-AI (88.3%; 95% CI, 79.2%-94.9%) was significantly higher than the 3 previously published models (P < .001) and similar to human experts., Conclusions and Relevance: In this study, SCORE-AI achieved human expert level performance in fully automated interpretation of routine EEGs. Application of SCORE-AI may improve diagnosis and patient care in underserved areas and improve efficiency and consistency in specialized epilepsy centers.

Patients with epilepsy (PWE) may experience seizure emergencies including acute repetitive seizures despite chronic treatment with daily antiseizure medications. Seizures may adversely impact routine daily activities and/or healthcare utilization and may impair the quality of life of patients with epilepsy and their caregivers. Seizures often occur at home, school, or work in a community setting. Appropriate treatment that is readily accessible for patients with seizure urgencies and emergencies is essential outside the hospital setting. When determining the best acute antiseizure therapy for PWE, clinicians need to consider all of the available rescue medications and their routes of administration including the safety and efficacy profiles. Benzodiazepines are a standard of care as a rescue therapy, yet there are several misconceptions about their use and safety. Reevaluating potential misconceptions and formulating best practices are necessary to maximize usage for each available option of acute therapy. We examine common beliefs associated with traditional use of acute seizure therapies to refute or support them based on the current level of evidence in the published literature., Competing Interests: 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., (© 2023 The Authors.)

Summary: The responsive neurostimulator continuously monitors the electrocorticogram. It delivers short bursts of high-frequency electrical stimulation when personalized patterns are detected. Intracranial EEG recording including electrocorticography is susceptible to artifacts, albeit at a lesser frequency compared with scalp recording. The authors describe a novel case of a patient with focal epilepsy, bitemporal responsive neurostimulation, and seizures without self-awareness manifest as focal impaired awareness seizures adversely affecting memory. At follow-up evaluation, the patient reported being clinically seizure-free although a single long episode was detected using the Patient Data Management System over the course of 3 years. Initial review identified a left-sided rhythmic discharge with a bilateral spatial field of involvement. In response to detection, the responsive neurostimulation delivered a series of five electrical stimulations. On further review, the patient recalled undergoing cervical radiofrequency ablation, which coincided with the appearance of the "electrographic seizure." Extrinsic electrical artifact involving monomorphic nonevolving waveforms confirmed electrical artifact identified and treated by responsive neurostimulation as an epileptic seizure. On rare occasion, implanted electrical devices may lead to misdiagnosis and mistreatment of patients because of intracranial artifact., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 by the American Clinical Neurophysiology Society.)

Neuromodulation in epilepsy is a proven treatment for people with drug-resistant focal epilepsy. Dual device therapies are increasingly utilized in people with drug-resistant epilepsy. Vagus nerve stimulation (VNS) and deep brain stimulation (DBS) target the thalamus involving the primary neurobiological network in patients with genetic generalized epilepsy (GGE). We report a novel case of combined neuromodulation in a patient with drug-resistant GGE who achieved a partial response with seizure reduction after VNS implantation yet following VNS-DBS polyneurostimulation gradually achieved prolonged seizure freedom. We speculate that by combining the indirect activating effects of VNS with the direct inhibitory effects of DBS, this may provide synergy to thalamic modulated networks. We hypothesize a "rational polytherapy" may exist in some patients with GGE undergoing dual neuromodulation., (© 2023 International League Against Epilepsy.)

Focal cortical dysplasia (FCD) is a congenital developmental malformation and is one of the leading causes of drug-resistant focal epilepsy (DRFE). Although focal epilepsies traditionally have been regarded as acquired disorders, increasing evidence suggests a substantial genetic contribution to the pathogenesis of focal structural epilepsies, including FCDs. Variations in the Dishevelled, Egl-10, and domain-containing protein 5 (DEPDC5) have recently emerged as a causative gene mutation in familial focal epilepsies associated with FCD type 2a, including bottom-of-sulcus dysplasia (BOSD). We present the case of a 20-year-old man with DRFE, positive for DEPDC5 c.1555C>T (p.GIn519*) heterozygous pathogenic variant. Initial 3T brain MRI was unrevealing, but subsequent 7T MRI including 7T edge-enhancing gradient echo revealed a left superior frontal sulcus BOSD concordant with the electroclinical data. The patient underwent treatment with MR-guided laser interstitial thermal ablation of the left frontal BOSD without intracranial EEG monitoring (skipped candidate), resulting in a seizure-free outcome of 9 months since the last follow-up. Our case highlights the real-world application of summative information obtained through advancements in epilepsy genetic testing, minimally invasive surgeries, and ultra-high field MRI, allowing us to provide a safe and effective treatment for a patient with a genetic DRFE., (© 2023 American Academy of Neurology.)

The 3D edge-enhancing gradient-echo (EDGE) MR imaging sequence offers superior contrast-to-noise ratio in the detection of focal cortical dysplasia. EDGE could benefit from 7T MR imaging but also faces challenges such as image inhomogeneity and low acquisition efficiency. We propose an EDGE-MP2RAGE sequence that can provide both EDGE and T1-weighted contrast, simultaneously, improving data-acquisition efficiency. We demonstrate that with sequence optimization, EDGE images with sufficient uniformity and T1-weighted images with high gray-to-white matter contrast can be achieved., (© 2023 by American Journal of Neuroradiology.)

Objective: Magnetic resonance-guided laser interstitial thermal therapy (MRLiTT) for treating temporal lobe epilepsy has recently gained popularity. We aimed to investigate the predictive value of pre-and post-MRLiTT epileptiform discharges (EDs) on intraoperative electrocorticography (iECoG) in seizure outcomes for patients with mesial temporal lobe epilepsy (mTLE)., Methods: We conducted a pilot, prospective single-center cohort study on seven consecutive patients with mTLE that underwent MRLiTT. Pre- and post-MRLiTT iECoG was performed using a 1x8 contact depth electrode along the same trajectory used for the laser catheter., Results: The responders had a robust reduction in ED frequency compared to pre-MRLiTT iECoG (86% vs 13%, p < 0.01). Clinical characteristics, including risk factors for epilepsy, duration of epilepsy, presence of mesial temporal lobe sclerosis, prior intracranial monitoring, the absolute frequency of pre- or post-MRLiTT EDs, and ablation volume were not significantly associated with responder status., Conclusions: This is the first demonstration that intraoperative reduction in EDs during mesial temporal lobe MRLiTT may potentially predict seizure outcomes and may serve as an intraoperative biomarker for satisfactory ablation. However, larger prospective studies are needed to confirm our findings and evaluate the utility of iECoG during MRLiTT., Significance: iECoG during mesial temporal lobe MRLiTT may help assess seizure outcomes., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Purpose: Electroencephalogram is used for prognostication and diagnosis in critically ill patients and is vital in developing clinical management algorithms. Unique waveforms on EEG may distinguish neurological disorders and define a potential for seizures. To better characterize zeta waves, we sought to define their electroclinical spectrum., Methods: We performed a systematic review using MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Review [through Ovid], Scopus, Science Citation Index Expanded and Emerging Sources Citation Index [through the Web of Science], and Epistemonikos. Grey literature resources were searched., Results: Five hundred thirty-seven articles were identified. After excluding duplicates and reviewing titles, abstracts, and bodies and bibliographies of articles, four studies reported 64 cases describing data from patients with zeta waves, with a prevalence of 3 to 4%. Various and often incomplete clinical, neuroimaging, and EEG data were available. 57 patients (89.1%) had a focal cerebral lesion concordant with the location of zeta waves on EEG. 26 patients (40.6%) had clinical seizures, all but one being focal onset. Thirteen patients (20%) had epileptiform activity on EEG. Typically, zeta waves were located in the frontal head regions, often with generalized, frontal, predominant, rhythmic delta activity and associated with focal EEG suppression., Conclusions: Zeta waves frequently represent an underlying focal structural lesion. Their presence suggests a heightened risk for seizures. The small number of retrospective cases series in the literature reporting zeta waves might be an underrepresentation. We suggest a need for prospective studies of cEEG in critically ill patients to determine their clinical significance., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 by the American Clinical Neurophysiology Society.)

Background: Epilepsy represents an essential component of Parry Romberg syndrome (PRS). This study aimed to identify clinical factors that influence the development of epilepsy and drug-resistant epilepsy (DRE) in PRS., Methods: We retrospectively reviewed the medical records of eighty patients with PRS. Data including the age of onset for PRS, history of seizures, use and timing of immunotherapy, antiseizure medication use, and EEG and brain imaging findings were reviewed. For comparison with the patients with epilepsy (PRSe+) group, we selected 18 age and sex-matched controls from the patient without epilepsy (PRSe-) cohort using propensity score matching., Results: Eighteen (22.5%) had epilepsy: 12 were female, and the median age was 14.5 years (range = 6-48 years). Eleven patients developed DRE. The median latency between the onset of cutaneous manifestations and diagnosis and timing and use of immunotherapy was similar between the PRSe + and PRSe- groups. Intracranial abnormalities were commonly seen in the PRSe + group (16 vs. 2, p < 0.01). White matter disease and ipsilateral atrophy were common among the PRSe + group. Timing and use of immunotherapy, epileptiform discharges, and brain imaging abnormalities did not differ between those with DRE and without., Conclusions: The presence and degree of severity of ipsilateral brain abnormalities are risk factors for the development of epilepsy in PRS but not factors in predicting drug resistance. The timing of immunotherapy did not influence the development of PRSe + or DRE. Prospective studies are needed to identify biomarkers for epilepsy and assess the role of immunotherapy on seizure outcomes in PRSe + ., (Copyright © 2022. Published by Elsevier B.V.)

Temporal lobe epilepsy is the most common form of focal epilepsy and is frequently resistant to antiseizure medication. Non-invasive biomarkers are crucial when resective epilepsy surgery is considered in order to guide diagnostic work-up and management. Interictal epileptiform discharges, when concordant with ictal EEG recording and a focal abnormality on functional imaging or anatomic MRI in patients with temporal lobe epilepsy, portend a favorable outcome with resective or ablative surgery. An interictal non-epileptiform feature on EEG believed to have the same localizing potential as epileptiform discharges is temporal intermittent rhythmic delta activity (TIRDA). The precise localization of TIRDA has been a subject of debate, but has been associated with seizures that arise from the temporal region. We report a 64-year-old female who underwent unsuccessful right anterior temporal lobectomy for drug-resistant focal epilepsy, suspected to originate from the right temporal lobe. Subsequent video-EEG monitoring revealed right, greater than left, TIRDA and interictal epileptiform discharges arising from the temporal regions bilaterally, despite a generous temporal lobectomy demonstrated by brain MRI. Further, using EEG source localization, we identified TIRDA using scalp EEG in sensor space, localized to the ipsilateral orbitofrontal region. We discuss the proposed localization of TIRDA in this case and address the importance of characterizing TIRDA in the presurgical evaluation of patients with epilepsy.

Objective: Although stereotactic EEG (sEEG) has become a widely used intracranial EEG technique, the significance of subclinical seizures (SCS) recorded on sEEG is unclear and studies examining this finding on sEEG are limited. We investigated (1) the prevalence of SCS in patients undergoing sEEG and clinical factors associated with their presence, (2) how often the subclinical seizure onset zone (SOZ) colocalizes with clinical SOZ, (3) the association of SCS and surgical outcomes, and (4) the influence of resection of the subclinical SOZ on surgical outcome., Methods: We reviewed all patients who underwent intracranial monitoring with sEEG at our institution from 2015 through 2020 (n=169). Patient and seizure characteristics were recorded, as was concordance of subclinical and clinical seizures and post-surgical outcomes., Results: SCS were observed during sEEG monitoring in 84 of 169 patients (50%). There was no difference in the prevalence of SCS based on imaging abnormalities, temporal vs extratemporal SOZ, number of electrodes, or pathology. SCS were more common in females than males (62% vs 40%, p=0.0054). SCS had complete concordance with clinical SOZ in 40% of patients, partial concordance in 29%, overlapping in 19%, and discordant in 12%. Eighty-three patients had surgery, 44 of whom had SCS. There was no difference in excellent outcome (ILAE 12 or 2) based on the presence of SCS or SCS concordance with clinical SOZ; however, there were improved outcomes in patients with complete resection of the subclinical SOZ compared with patients with incomplete resection (p =0.013)., Significance: These findings demonstrate that SCS are common during sEEG and colocalize with the clinical SOZ in most patients. Discordance with clinical SOZ does not necessarily predict poor surgical outcome; rather, complete surgical treatment of the subclinical SOZ correlates with excellent outcome. For unclear reasons, subclinical seizures occurred more commonly in females than males., 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 © 2022. Published by Elsevier Ltd.)

Objective: The authors hypothesized that the proximity of deep brain stimulator contacts to the anterior thalamic nucleus-mammillothalamic tract (ANT-MMT) junction determines responsiveness to treatment with ANT deep brain stimulation (DBS) in drug-resistant epilepsy and conducted this study to test that hypothesis., Methods: This retrospective study evaluated patients who had undergone ANT DBS electrode implantation and whose devices were programmed to stimulate nearest the ANT-MMT junction based on direct MRI visualization. The proximity of the active electrode to the ANT and the ANT-MMT junction was compared between responders (≥ 50% reduction in seizure frequency) and nonresponders. Linear regression was performed to assess the percentage of seizure reduction and distance to both the ANT and the ANT-MMT junction., Results: Four (57.1%) of 7 patients had ≥ 50% reduction in seizures. All 4 responders had at least one contact within 1 mm of the ANT-MMT junction, whereas the 3 patients with < 50% seizure improvement did not have a contact within 1 mm of the ANT-MMT junction. Additionally, the 4 responders demonstrated contact positioning closer to the ANT-MMT junction than the 3 nonresponders (mean distance from MMT: 0.7 mm on the left and 0.6 mm on the right in responders vs 3.0 mm on the left and 2.3 mm on the right in nonresponders). However, proximity of the electrode contact to any point in the ANT nucleus did not correlate with seizure reduction. Greater seizure improvement was correlated with a contact position closer to the ANT-MMT junction (R2 = 0.62, p = 0.04). Seizure improvement was not significantly correlated with proximity of the contact to any ANT border (R2 = 0.24, p = 0.26)., Conclusions: Obtained using a combination of direct visualization and targeted programming of the ANT-MMT junction, data in this study support the hypothesis that proximity to the ANT alone does not correlate with seizure reduction in ANT DBS, whereas proximity to the ANT-MMT junction does. These findings support the importance of direct targeting in ANT DBS, as well as imaging-informed programming. Additionally, the authors provide supportive evidence for future prospective trials using ANT-MMT junction for direct surgical targeting.

Summary: Ambulatory EEG (AEEG) devices offer portable, multichannel, digital EEG recording with or without video in the patient's natural environment. The technology applied for AEEG recording is like the technology for routine EEG and inpatient long-term video-EEG monitoring but designed to be compact and wearable. Computer-based AEEG technology is well-suited to digital recording, signal processing, and visual display. However, acquiring interpretable EEG outside of the hospital setting presents its own technical challenges. Published guidelines have established technical standards for performing routine EEG and inpatient video-EEG monitoring, but technical standards for AEEG are lacking. Therefore, this guideline provides minimal technical standards for the performance of AEEG which are essential to ensure the quality of studies for clinical and research practice. We expect these minimum standards to evolve over time with improved performance and advances in the technology., (Copyright © 2022 by the American Clinical Neurophysiology Society.)

Purpose: This study examines the safety and effectiveness of brain-responsive neurostimulation (RNS System) therapy in patients with refractory autoimmune-associated epilepsy (AAE)., Methods: We retrospectively reviewed 85 medical records of patients who were treated with the RNS System at the three Mayo Clinic sites to identify patients with AAE. We collected clinical data including demographics, epilepsy history, prior evaluations and treatment, RNS implantation and lead information, long term ambulatory electrocorticography (ECoG) data, and patient-reported seizure details. Inclusion criteria included: (1) confirmed neural antibodies, or absent/negative autoimmune panel with Antibody Prevalence in Epilepsy (APE2) score ≥ 4 and (2) at least 6 months of follow up after RNS implantation. The primary outcomes measured were patient-reported seizure frequencies at last follow-up as compared to baseline, ECoG long-episode frequencies, and adverse events following RNS implantation., Results: Of the 85 patients reviewed, nine (11 %) met the inclusion criteria. Three patients had GAD65 antibodies (mean serum titer = 816 ug/dl), one had Rasmussen's encephalitis (biopsy proven), and five had absent/negative neuronal antibody panel but APE scores were ≥ 4. Six out of nine patients (67 %) reported improvement in clinical seizure frequency, all reported improvements in seizure duration and intensity. Four of 9 patients (44 %) showed trends of decreasing frequency of prolonged periods of epileptiform activity over time. One patient (11 %) developed a superficial wound infection at the implant site., Conclusion: The findings from our study suggest that adjunctive treatment with the RNS System may be a safe option for patients with refractory AAE., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This educational topical review and Task Force report aims to address learning objectives of the International League Against Epilepsy (ILAE) curriculum. We sought to extract detailed features involving semiology from video recordings and interpret semiological signs and symptoms that reflect the likely localization for focal seizures in patients with epilepsy. This glossary was developed by a working group of the ILAE Commission on Diagnostic Methods incorporating the EEG Task Force. This paper identifies commonly used terms to describe seizure semiology, provides definitions, signs and symptoms, and summarizes their clinical value in localizing and lateralizing focal seizures based on consensus in the published literature. Video-EEG examples are included to illustrate important features of semiology in patients with epilepsy.