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Background: To describe a rare seizure semiology originating from a hypothalamic hamartoma in a child, along with unusual ictal onset and connectivity pattern, and provide a review of the pathophysiology of epilepsy associated with hypothalamic hamartoma and management., Methods: A detailed retrospective chart review and literature search were performed using Pubmed and Embase., Results: We present a case of a three-year-old male who presented with dyscognitive seizures with onset at age 22 months. Stereoelectroencephalography exploration confirmed the onset in hypothalamic hamartoma with rapid propagation to the temporal-parietal-occipital association cortex and precuneus. The patient's epilepsy was cured with laser ablation of the hamartoma., Conclusion: Published literature mostly describes a more anterior frontal or temporal epileptic network with primarily gelastic seizures being the hallmark type of seizures associated with hypothalamic hamartoma. We highlight a rare posterior cortex network with an atypical presentation of focal nonmotor seizures with impaired awareness in the setting of a hypothalamic hamartoma. Stereotactic laser ablation of the hamartoma rendered seizure freedom. Early diagnosis and appropriate treatment can lead to seizure freedom., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To predict one-year seizure freedom, using a combination of relevant clinical variables, following stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy in a series of 101 patients., Methods: Eight predictors of seizure freedom were selected based on their association with medial temporal lobe epilepsy: (1) MRI evidence of mesial temporal sclerosis (MTS); (2) unitemporal interictal epileptiform discharges; (3) absence of generalized tonic-clonic seizures; (4) history of febrile seizures; (5) onset of epilepsy ≤16 years; (6) absence of an auditory, visual, or vertiginous aura; and (7) unitemporal ictal onset; (8) unitemporal PET hypometabolism. We compared four multivariate models: "MTS," using just evidence of MTS; "FULL," using all eight binary predictors; "AIC" using backwards selection of variables; and "SCORE," using a 0-to-8-point ordinal score awarding one point for each binary predictor., Results: In univariate analysis, significant predictors for seizure freedom were evidence of mesial temporal sclerosis (p = 0.011, Fisher exact) and unitemporal interictal discharges (p = 0.005). For multivariate prediction (using leave one-out cross-validation), the ordinal SCORE model had a significantly higher area under the curve (AUC 0.70) than the other three models: MTS (AUC 0.54, p = 0.002, Delong's test), FULL (AUC 0.62, p = 0.003), or AIC (AUC 0.53, p < 0.001)., Interpretation: An ordinal score incorporating eight independent binary clinical variables predicted seizure freedom better on novel data than a model using MTS alone, a full multivariate model, or a backwards selected model. The ordinal score model represents a simple clinical heuristic to identify which patients should be offered minimally invasive laser surgery., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

The piriform cortex is recognized as highly epileptogenic in rodents, yet its electrophysiological role in human epilepsy remains understudied. Recent surgical outcomes have suggested potential benefits in resecting the piriform cortex for cases of medial temporal lobe epilepsy. However, little is known about its electrophysiological activity in human epilepsy. This case-series study aimed to explore the electrophysiological role of the piriform cortex within the epileptogenic network among patients with suspected temporal lobe epilepsy. Participants were recruited from Emory University Hospital or Children's Healthcare of Atlanta, with non-lesional frontotemporal or temporal lobe hypotheses, undergoing stereoelectroencephalographic studies. Specifically, focus was placed on patients with one or more electrode contacts in the piriform cortex. Primary objectives included determining piriform cortex involvement within the electrophysiologically defined epileptogenic network and assessing the effects of electrical stimulation. Twenty-two patients were included in the study. Notably, only one patient exhibited piriform cortex involvement at seizure onset, associated with an olfactory aura. Two patients showed early piriform cortex involvement, while others displayed late or no involvement. Electrical stimulation of the piriform cortex induced after-discharges in three patients and replicated a habitual seizure in one. These findings present a contrast to surgical outcome studies, suggesting that the piriform cortex may not typically play a significant role in the epileptogenic network among patients with non-lesional temporal lobe epilepsy., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Summary: Stereoelectroencephalography (SEEG) has emerged as a transformative tool in epilepsy surgery, shedding light on the complex network dynamics involved in focal epilepsy. This review explores the role of SEEG in elucidating the role of deep brain structures, namely the basal ganglia and thalamus, in epilepsy. SEEG advances understanding of their contribution to seizure generation, propagation, and control by permitting precise and minimally invasive sampling of these brain regions. The basal ganglia, comprising the subthalamic nucleus, globus pallidus, substantia nigra, and striatum, have gained recognition for their involvement in both focal and generalized epilepsy. Electrophysiological recordings reveal hyperexcitability and increased synchrony within these structures, reinforcing their role as critical nodes within the epileptic network. Furthermore, low-frequency and high-frequency stimulation of the basal ganglia have demonstrated potential in modulating epileptogenic networks. Concurrently, the thalamus, a key relay center, has garnered prominence in epilepsy research. Disrupted thalamocortical connectivity in focal epilepsy underscores its significance in seizure maintenance. The thalamic subnuclei, including the anterior nucleus, centromedian, and medial pulvinar, present promising neuromodulatory targets, suggesting pathways for personalized epilepsy therapies. The prospect of multithalamic SEEG and thalamic SEEG stimulation trials has the potential to revolutionize epilepsy management, offering tailored solutions for challenging cases. SEEG's ability to unveil the dynamics of deep brain structures in epilepsy promises enhanced and personalized epilepsy care in our new era of precision medicine. Until deep brain SEEG is accepted as a standard of care, a rigorous informed consent process remains paramount for patients for whom such an exploration is proposed., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 by the American Clinical Neurophysiology Society.)

Summary: Stereoelectroencephalography is an established, hypothesis-driven method for investigating refractory epilepsy. There are special considerations and some limitations that apply to children who undergo stereoelectroencephalography. A key principle in stereoelectroencephalography is taking an individualized approach to investigating refractory epilepsy. A crucial factor for success in a personalized pediatric epilepsy surgery is understanding some of the fundamental and unique aspects of it, including, but not limited to, diverse etiology, epilepsy syndromes, maturation, and age-related characteristics as well as neural plasticity. Such features are reflected in the ontogeny of semiology and electrophysiology. In addition, special considerations are taken into account during cortical stimulation in children. Stereoelectroencephalography can guide a tailored surgical intervention where it is sufficient to render the patient seizure-free but it also lessens collateral damage with a minimum or no functional deficit. Epilepsy surgery outcomes remain stagnant despite advances in noninvasive testing modalities. A stereoelectroencephalography "way of thinking" and guided mentorship may influence outcomes positively., Competing Interests: The authors have no funding or conflicts of interest to disclose...pp-, (Copyright © 2024 by the American Clinical Neurophysiology Society.)

Purpose: Central sulcus localization is undertaken intraoperatively with subdural electrodes through a phase reversal technique using somatosensory evoked potentials from sensorimotor cortices. Extraoperative central sulcus localization using stereoelectroencephalography has not been described previously., Methods: Six pediatric patients (aged 12-18 years, 50% females) were investigated with stereoelectroencephalography. Peripheral median and posterior tibial nerve stimulation were performed while recording somatosensory evoked potentials from stereoelectroencephalography electrodes., Results: Central sulcus was successfully localized by this novel method, and this was further supplemented by cortical stimulation data., Conclusions: This is the first report of somatosensory evoked potentials gained using stereoelectroencephalography in primary motor and sensory cortices. This can further supplement other data for safe surgical resection in the eloquent cortex., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 by the American Clinical Neurophysiology Society.)

The conventional intracarotid amobarbital (Wada) test has been used to assess memory function in patients being considered for temporal lobe epilepsy (TLE) surgery. Minimally invasive approaches that target the medial temporal lobe (MTL) and spare neocortex are increasingly used, but a knowledge gap remains in how to assess memory and language risk from these procedures. We retrospectively compared results of two versions of the Wada test, the intracarotid artery (ICA-Wada) and posterior cerebral artery (PCA-Wada) approaches, with respect to predicting subsequent memory and language outcomes, particularly after stereotactic laser amygdalohippocampotomy (SLAH). We included all patients being considered for SLAH who underwent both ICA-Wada and PCA-Wada at a single institution. Memory and confrontation naming assessments were conducted using standardized neuropsychological tests to assess pre- to post-surgical changes in cognitive performance. Of 13 patients who initially failed the ICA-Wada, only one patient subsequently failed the PCA-Wada (p=0.003, two-sided binomial test with p 0 =0.5) demonstrating that these tests assess different brain regions or networks. PCA-Wada had a high negative predictive value for the safety of SLAH, compared to ICA-Wada, as none of the patients who underwent SLAH after passing the PCA-Wada experienced catastrophic memory decline (0 of 9 subjects, p <.004, two-sided binomial test with p 0 =0.5), and all experienced a good cognitive outcome. In contrast, the single patient who received a left anterior temporal lobectomy after failed ICA- and passed PCA-Wada experienced a persistent, near catastrophic memory decline. On confrontation naming, few patients exhibited disturbance during the PCA-Wada. Following surgery, SLAH patients showed no naming decline, while open resection patients, whose surgeries all included ipsilateral temporal lobe neocortex, experienced significant naming difficulties (Fisher's exact test, p <.05). These findings demonstrate that (1) failing the ICA-Wada falsely predicts memory decline following SLAH, (2) PCA-Wada better predicts good memory outcomes of SLAH for MTLE, and (3) the MTL brain structures affected by both PCA-Wada and SLAH are not directly involved in language processing.

Objectives: Corpus callosotomy (CC) is used to reduce seizures, primarily in patients with generalized drug-resistant epilepsy (DRE). The invasive nature of the procedure contributes to underutilization despite its potential superiority to other palliative procedures. The goal of this study was to use a multi-institutional epilepsy surgery database to characterize the use of CC across participating centers., Methods: Data were acquired from the Pediatric Epilepsy Research Consortium (PERC) Surgery Database, a prospective observational study collecting data on children 0-18 years referred for surgical evaluation of DRE across 22 U.S. pediatric epilepsy centers. Patient, epilepsy, and surgical characteristics were collected across multiple CC modalities. Outcomes and complications were recorded and analyzed statistically., Results: Eighty-three patients undergoing 85 CC procedures at 14 participating epilepsy centers met inclusion criteria. Mean age at seizure onset was 2.3 years (0-9.4); mean age for Phase I evaluation and surgical intervention were 9.45 (.1-20) and 10.46 (.2-20.6) years, respectively. Generalized seizure types were the most common (59%). Complete CC was performed in 88%. The majority of CC procedures (57%) were via open craniotomy, followed by laser interstitial thermal therapy (LiTT) (20%) and mini-craniotomy/endoscopic (mc/e) (22%). Mean operative times were significantly longer for LiTT, whereas mean estimated blood loss was greater in open cases. Complications occurred in 11 cases (13%) and differed significantly between surgical techniques (p < .001). There was no statistically significant difference in length of postoperative stay across approaches. Mean follow-up was 12.8 months (range 1-39). Favorable Engel outcomes were experienced by 37 (78.7%) of the patients who underwent craniotomy, 10 (58.8%) with LiTT, and 12 (63.2%) with mc/e; these differences were not statistically significant., Significance: CC is an effective surgical modality for children with DRE. Regardless of surgical modality, complication rates are acceptable and seizure outcomes generally favorable. Newer, less-invasive, surgical approaches may lead to increased adoption of this efficacious therapeutic option for pediatric DRE., (© 2023 International League Against Epilepsy.)

Objective: This study assesses current practices and outcomes of epilepsy surgery in children with a genetic etiology. It explores the pre-surgical workup, types of surgeries, and post-surgical outcomes in a broad array of disorders., Methods: Patients ≤18 years who completed epilepsy surgery and had a known genetic etiology prior to surgical intervention were extrapolated from the Pediatric Epilepsy Research Consortium (PERC) surgery database, across 18 US centers. Data were assessed univariably by neuroimaging and EEG results, genetic group (structural gene, other gene, chromosomal), and curative intent. Outcomes were based on a modified International League Against Epilepsy (ILAE) outcome score., Results: Of 81 children with genetic epilepsy, 72 % had daily seizures when referred for surgery evaluation, which occurred a median of 2.2 years (IQR 0.3, 5.2) after developing drug resistance. Following surgery, 68 % of subjects had >50 % seizure reduction, with 33 % achieving seizure freedom [median follow-up 11 months (IQR 6, 17). Seizure freedom was most common in the monogenic structural group, but significant palliation was present across all groups. Presence of a single EEG focus was associated with a greater likelihood of seizure freedom (p=0.02)., Significance: There are meaningful seizure reductions following epilepsy surgery in the majority of children with a genetic etiology, even in the absence of a single structural lesion and across a broad spectrum of genetic causes. These findings highlight the need for expedited referral for epilepsy surgery and support of a broadened view of which children may benefit from epilepsy surgery, even when the intent is palliative., Competing Interests: Declaration of Competing Interest Allyson Alexander, MD is a consultant for NuXceland. All additional authors report no declarations of interest., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives: Epilepsy education has been transformed over the past 2 decades, leading to a need for structured formative assessment tools. The American Epilepsy Society developed the Epilepsy Fellowship In-Training Examination (EpiFITE) to provide high-quality formative assessment for fellows, to stimulate program improvement, and to guide future learning and teaching. The aim of this study was to explore validity evidence for the EpiFITE in meeting these goals., Methods: Validity evidence was sought from multiple sources. The content of the examination was linked to the American Board of Psychiatry and Neurology blueprint for initial certification in epilepsy, and items were developed by trained experts. Internal structure was studied using internal consistency and item analysis. Surveys of fellows and fellowship directors focused on the examination experience (response process) and how results influenced fellow assessment, future learning, and program improvement (relationship to other variables and consequences)., Results: The EpiFITE was first administered in 2020, with 172 examinees from 67 programs. By 2022 (year 3), the EpiFITE was completed by 195 epilepsy fellows from 77 programs. The overall mean score of the examination was stable from year to year, and the committee predicted the difficulty of individual items with a high degree of accuracy. The examination had high internal consistency (Cronbach α 0.76-0.81). The median item discrimination index ranged from 0.17 in 2020 to 0.21 in 2022. Discrimination indices were lower (mean ≤0.10) for items that were either very easy or very difficult and significantly higher (mean >0.20) for other items. Program directors and epilepsy fellows agreed the examination questions were appropriate and agreed that the EpiFITE helped them identify areas for self-directed learning. Program directors also found the examination helpful in identifying areas of strength and areas for improvement within their programs., Discussion: There are several sources of evidence of the quality and validity of the EpiFITE. By exploring this validity evidence, we have identified several best practices in the development and evaluation of a subspecialty examination, and this experience could be helpful for developers of in-training examinations in other subspecialties., Competing Interests: The authors report no disclosures relevant to the manuscript. Go to Neurology.org/NE for full disclosures., (© 2023 American Academy of Neurology.)

Competing Interests: Declaration of competing interest We confirm that the authors have no conflict of interest or funding related to this manuscript.

The piriform cortex (PC) is part of the olfactory system, principally receiving input from the lateral olfactory tract and projecting to downstream components of the olfactory network, including the amygdala. Based on preclinical studies, PC is vulnerable to injury and can be easily kindled as an onset site for seizures. While the role of PC in human epilepsy has been studied indirectly and the subject of speculation, cases of demonstrated PC seizure onset from direct intracranial recording are rare. We present a pediatric patient with drug-resistant focal reflex epilepsy and right mesial temporal sclerosis with habitual seizures triggered by coconut aroma. The patient underwent stereoelectroencephalography with implantation of olfactory cortices including PC, through which we identified PC seizure onset, mapped high-frequency activity associated with presentation of olfactory stimuli and performance on cognitive tasks, and reproduced habitual seizures via cortical stimulation of PC. Coconut odor did not trigger seizures in our work with the patient. Surgical workup resulted in resection of the patient's right amygdala, PC, and mesial temporal pole, following which she has been seizure free for 20 months without functional decline in cognition or smell. Histological findings from resected tissue showed astrogliosis and subpial gliosis.

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common pediatric epilepsy comorbidities. Treating ADHD in the context of epilepsy can be overwhelming for parents and clinicians. Current frontline treatment for ADHD is stimulant medication. However, some parents of pediatric patients with epilepsy have concerns about adding additional medication to their child's epilepsy regimen and/or about adverse effects of stimulant medication. Non-medication ADHD treatments including psychosocial interventions and ketogenic diet have also shown success in improving ADHD symptoms. Our focused review provides an easy-to-use guide for clinicians on ADHD interventions and combinations of interventions for pediatric patients with epilepsy and ADHD. Our guide includes information from 8 electronic databases for peer-reviewed, English language studies of psychosocial treatments for youth with epilepsy and ADHD. One hundred eight studies were selected based on inclusion criteria (21 systematic reviews, 12 meta-analyses, 8 literature reviews, 6 population surveys, 31 clinical trials, 20 cross-sectional studies, and 10 retrospective reviews). Results indicated that stimulant medication is a frontline treatment for ADHD symptoms in youth with epilepsy, with important caveats and alternatives., 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., (Published by Elsevier Inc.)

Purpose: Corticocortical evoked potentials (CCEPs) resulting from single pulse electrical stimulation are increasingly used to understand seizure networks, as well as normal brain connectivity. However, we observed that when using depth electrodes, traditional measures of CCEPs amplitude using a referential montage can be falsely localizing, often to white matter., Methods: We pooled 27 linear electrode arrays targeting the amygdala, hippocampus, or cingulate cortex from eight participants. Using postoperative imaging, we classified contacts as being in gray matter, white matter, or bordering each and measured the amplitude using the root-mean-squared deviation from baseline in a referential, common average, bipolar, or Laplacian montage., Results: Of 27 electrode contacts, 25 (93%) had a significantly higher mean amplitude when in gray matter than in white matter using a Laplacian montage, which was significantly more than the 12 of 27 electrodes (44%) when using a referential montage ( P = 0.0003, Fisher exact test). The area under the curve for a receiver operating characteristic classifying contacts as gray or white matter was significantly higher for either the Laplacian (0.79) or the bipolar (0.72) montage when compared with either the common average (0.56) or the referential (0.51) montage ( P ≤ 0.005, bootstrap)., Conclusions: Both the Laplacian and bipolar montages were superior to the common average or referential montage in localizing CCEPs to gray matter. These montages may be more appropriate for interpreting CCEPs when using depth electrodes than the referential montage, which has typically been used in prior studies of CCEPs with subdural grids., Competing Interests: N. P. Pedersen has served as a consult and is on the scientific advisory board of Dixi Medical USA. D. L. Drane has served as a consultant to Neuropace and serves as the Core Lab Director of the Clinical Study of Stereotactic Laser Ablation of Temporal Lobe Epilepsy (SLATE) conducted by Medtronic. These companies manufacture products related to research described in this article. The terms of these arrangements have been reviewed and approved by Emory University in accordance with its conflict of interest policies. The remaining authors have no conflicts of interest to disclose., (Copyright © 2020 by the American Clinical Neurophysiology Society.)

Roughly two-thirds of all people report having experienced déjà vu-the odd feeling that a current experience is both novel and a repeat or replay of a previous, unrecalled experience. Reports of an association between déjà vu and seizure aura symptomatology have accumulated for over a century, and frequent déjà vu is also now known to be associated with focal seizures, particularly those of a medial temporal lobe (MTL) origin. A longstanding question is whether seizure-related déjà vu has the same basis and is the same subjective experience as non-seizure déjà vu. Survey research suggests that people who experience both seizure-related and non-seizure déjà vu can often subjectively distinguish between the two. We present a case of a person with a history of focal MTL seizures who reports having experienced both seizure-related and non-seizure common déjà vu, though the non-seizure type was more frequent during this person's youth than it is currently. The patient was studied with a virtual tour paradigm that has previously been shown to elicit déjà vu among non-clinical, young adult participants. The patient reported experiencing déjà vu of the common non-seizure type during the virtual tour paradigm, without associated abnormalities of the intracranial EEG. We situate this work in the context of broader ongoing projects examining the subjective correlates of seizures. The importance for memory research of virtual scenes, spatial tasks, virtual reality (VR), and this paradigm for isolating familiarity in the context of recall failure are discussed., 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 © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Electrographic characteristics (extreme delta brush, posterior dominant rhythm and slow waves) may predict outcomes in anti-NMDA receptor encephalitis (NMDARE). However, whether changes in EEG sleep architecture predict outcomes are unknown. We examine electrophysiological characteristics including sleep architecture in a pediatric NMDARE population and correlate with outcomes at one year., Methods: Retrospective chart and EEG review was performed in pediatric NMDARE patients at a single center. Patients with first EEGs available within 48 h of admission, prior to treatment, and one-year follow-up data were included. EEGs were independently reviewed by two epileptologists, and a third when disagreement occurred. Clinical outcomes included modified Rankin scale (mRS) at one year., Results: Nine patients (6 females) (range 1.9-16.7 years) were included. Five of nine patients had loss of posterior dominant rhythm (PDR) and three of nine patients had absent sleep architecture. Loss of PDR correlated with a worse mRS score at one year (2.8 versus 0.5, p = 0.038). Loss of PDR and loss of sleep architecture was associated with increased inpatient rehabilitation stay and in higher number of immunotherapy treatments administered. In multivariate analysis, absence of sleep architecture (p = 0.028), absence of PDR (p = 0.041), and epileptiform discharges (p = 0.041) were predictors of mRS at one year., Conclusions: Loss of normal PDR, absence of sleep architecture, and epileptiform discharges are associated with worse outcomes at one year which has not been reported before. EEG characteristics may help prognosticate in NMDARE. Larger studies are needed to confirm these findings., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Perfusion patterns observed in Subtraction Ictal SPECT Co-registered to MRI (SISCOM) assist in focus localization and surgical planning for patients with medically intractable focal epilepsy. While the localizing value of SISCOM has been widely investigated, its relationship to the underlying electrophysiology has not been extensively studied and is therefore not well understood. In the present study, we set to investigate this relationship in a cohort of 70 consecutive patients who underwent ictal and interictal SPECT studies and subsequent stereo-electroencephalography (SEEG) monitoring for localization of the epileptogenic focus and surgical intervention. Seizures recorded during SEEG evaluation (SEEG seizures) were matched to semiologically-similar seizures during the preoperative ictal SPECT evaluation (SPECT seizures) by comparing the semiological changes in the course of each seizure. The spectral changes of the ictal SEEG with respect to interictal ones over 7 traditional frequency bands (0.1 to 150Hz) were analyzed at each SEEG site. Neurovascular (SEEG/SPECT) relations were assessed by comparing the estimated spectral power density changes of the SEEG at each site with the perfusion changes (SISCOM z-scores) estimated from the acquired SISCOM map at that site. Across patients, a significant correlation (p<0.05) was observed between spectral changes during the SEEG seizure and SISCOM perfusion z-scores. Brain sites with high perfusion z-score exhibited higher increased SEEG power in theta to ripple frequency bands with concurrent suppression in delta and theta frequency bands compared to regions with lower perfusion z-score. The dynamics of the correlation of SISCOM perfusion and SEEG spectral power from ictal onset to seizure end and immediate postictal period were also derived. Forty-six (46) of the 70 patients underwent resective epilepsy surgery. SISCOM z-score and power increase in beta to ripple frequency bands were significantly higher in resected than non-resected sites in the patients who were seizure-free following surgery. This study provides for the first time concrete evidence that both hyper-perfusion and hypo-perfusion patterns observed in SISCOM maps have strong electrophysiological underpinnings, and that integration of the information from SISCOM and SEEG can shed light on the location and dynamics of the underlying epileptic brain networks, and thus advance our anatomo-electro-clinical understanding and approaches to targeted diagnostic and therapeutic interventions., Competing Interests: Declarations of Competing Interest None., (Copyright © 2021. Published by Elsevier Inc.)

Mapping of cortical functions is critical for the best clinical care of patients undergoing epilepsy and tumor surgery, but also to better understand human brain function and connectivity. The purpose of this review is to explore existing and potential means of mapping higher cortical functions, including stimulation mapping, passive mapping, and connectivity analyses. We examine the history of mapping, differences between subdural and stereoelectroencephalographic approaches, and some risks and safety aspects, before examining different types of functional mapping. Much of this review explores the prospects for new mapping approaches to better understand other components of language, memory, spatial skills, executive, and socio-emotional functions. We also touch on brain-machine interfaces, philosophical aspects of aligning tasks to brain circuits, and the study of consciousness. We end by discussing multi-modal testing and virtual reality approaches to mapping higher cortical functions., Competing Interests: DD receives ongoing funding from Medtronic, Inc. to run a Core Analysis Lab for neuroimaging and cognitive testing in one of their FDA trials, these funds did not contribute in any form to his role in this paper. They were not involved in this paper in any manner, including study design, data collection, analysis, or interpretation, the writing of this article or the decision to submit it for publication. 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 Drane, Pedersen, Sabsevitz, Block, Dickey, Alwaki and Kheder.)

Background: The ictal examination is crucial for neuroanatomic localization of seizure onset, which informs medical and neurosurgical treatment of epilepsy. Substantial variation exists in ictal examination performance in epilepsy monitoring units (EMUs). We developed and implemented a standardized examination to facilitate rapid, reliable execution of all testing domains and adherence to patient safety maneuvers., Methods: Following observation of examination performance, root cause analysis of barriers, and review of consensus guidelines, an ictal examination was developed and disseminated. In accordance with quality improvement methodology, revisions were enacted following the initial intervention, including differentiation between pathways for convulsive and nonconvulsive seizures. We evaluated ictal examination fidelity, efficiency, and EMU staff satisfaction before and after the intervention., Results: We identified barriers to ictal examination performance as confusion regarding ictal examination protocol, inadequate education of the rationale for the examination and its components, and lack of awareness of patient-specific goals. Over an 18-month period, 100 ictal examinations were reviewed, 50 convulsive and 50 nonconvulsive. Ictal examination performance varied during the study period without sustained improvement for convulsive or nonconvulsive seizure examination. The new examination was faster to perform (0.8 vs 1.5 minutes). Postintervention, EMU staff expressed satisfaction with the examination, but many still did not understand why certain components were performed., Conclusion: We identified key barriers to EMU ictal assessment and completed real-world testing of a standardized, streamlined ictal examination. We found it challenging to reliably change ictal examination performance in our EMU; further study of implementation is warranted., (© 2020 American Academy of Neurology.)

The purpose of this review is to describe the functional anatomy of the precuneal cortex and outline some semiological features of precuneal seizures. The precuneal cortex is a structure that occupies the posterior medial portion of the parietal lobe, and it has broad cortical and subcortical connections. Neuroanatomical tracing, functional imaging, as well as electrical stimulation studies of humans and other primates have elucidated many complex integrative functions of the precuneus including visuo-spatial imagery, sensorimotor functions, and consciousness. Based on the understanding of its functions and connectivity, descriptions of potential seizure semiologies are hypothesized and compared to what is available in the literature. The latter is mostly in the form of case reports or case series. Seizures may involve simple or complex motor or sensory manifestations including abnormal eye movements, visual hallucinations, sensation of motion, or medial temporal-like seizures.

Objective: To study neural networks involved in hyperkinetic seizures (HKS) using ictal SPECT., Methods: We retrospectively identified 18 patients with HKS evaluated at the Cleveland Clinic between 2005 and 2015 with video-EEG monitoring and ictal SPECT. Semiology was confirmed by the consensus of 2 epileptologists' independent reviews and classified as type 1, 2, or 3 HKS. SPECT data were analyzed by 2 independent physicians using a z score of 1.5. Ictal hyperperfusion patterns for each group were analyzed visually and with SPM. Spatial normalization to Montreal Neurological Institute space for each patient's data was performed, followed by flipping of data from patients with left-sided ictal onset to the right side. Finally, an average z score map for each group was calculated., Results: Visual analysis and SPM identified different patterns of ictal hyperperfusion in the 3 subtypes of HKS. Type 1 seizures showed hyperperfusion in a more anteriorly located network involving the anterior insula, orbitofrontal cortex, cingulate, and anterior perisylvian region and rostral midbrain. Type 2 seizures were associated with hyperperfusion in a more caudally located network involving the orbitofrontal cortex, cingulate (middle and posterior), basal ganglia, thalami, and cerebellum. Type 3 seizures showed a mixed pattern of SPECT hyperperfusion involving the temporal pole and anterior perisylvian region., Conclusions: Each of the 3 different semiologic subtypes of HKS is associated with distinct patterns of hyperperfusion, providing further insight into the neural networks involved. This knowledge may inform placement of invasive EEG electrodes in patients with HKS semiology undergoing presurgical evaluation., (© 2020 American Academy of Neurology.)

Objective: Magnetic resonance imaging (MRI)-guided laser interstitial thermal therapy (MRg-LITT) is an alternative to open epilepsy surgery. We assess safety and effectiveness of MRg-LITT for extratemporal lobe epilepsy (ETLE) in patients who are considered less favorable for open resection., Methods: We retrospectively reviewed sequential cases of patients with focal ETLE who underwent MRg-LITT between 2012 and 2019. Epileptogenic zones were determined from standard clinical and imaging data ± stereoelectroencephalography (SEEG). Standard stereotactic techniques, MRI thermometry, and a commercial laser thermal therapy system were used for ablations. Anatomic MRI was used to calculate ablation volumes. Clinical outcomes were determined longitudinally., Results: Thirty-five patients with mean epilepsy duration of 21.3 ± 12.2 years underwent MRg-LITT for focal ETLE at a mean age 36.4 ± 12.7 years. A mean 2.59 ± 1.45 trajectories per patient were used to obtain ablation volumes of 8.8 ± 7.5 cm 3 . Mean follow-up was 27.3 ± 19.5 months. Of 32 patients with >12 months of follow-up, 17 (53%) achieved good outcomes (Engel class I + II) of whom 14 (44%) were Engel class I. Subgroup analysis revealed better outcomes for patients with lesional ETLE than for those who were nonlesional, multifocal, or who had failed prior interventions (P = .02). Of 13 patients showing favorable seizure-onset patterns (localized low voltage fast activity or rhythmic spiking on SEEG) prior to ablation, 9 (69%) achieved good outcomes, whereas only 3 of 11 (27%) who show other slower onset patterns achieved good outcomes. Minor adverse events included six patients with transient sensorimotor neurologic deficits and four patients with asymptomatic hemorrhages along the fiber tract. Major adverse events included one patient with a brain abscess that required stereotactic drainage and one patient with persistent hypothalamic obesity. Three deaths-two seizure-associated and one suicide-were unrelated to surgical procedures., Significance: MRI-guided laser interstitial thermal therapy (or MRg-LITT) was well-tolerated and yielded good outcomes in a heterogeneous group of ETLE patients. Lesional epilepsy and favorable seizure-onset patterns on SEEG predicted higher likelihoods of success., (© 2020 International League Against Epilepsy.)

Network neuroscience applied to epilepsy holds promise to map pathological networks, localize seizure generators, and inform targeted interventions to control seizures. However, incomplete sampling of the epileptic brain because of sparse placement of intracranial electrodes may affect model results. In this study, we evaluate the sensitivity of several published network measures to incomplete spatial sampling and propose an algorithm using network subsampling to determine confidence in model results. We retrospectively evaluated intracranial EEG data from 28 patients implanted with grid, strip, and depth electrodes during evaluation for epilepsy surgery. We recalculated global and local network metrics after randomly and systematically removing subsets of intracranial EEG electrode contacts. We found that sensitivity to incomplete sampling varied significantly across network metrics. This sensitivity was largely independent of whether seizure onset zone contacts were targeted or spared from removal. We present an algorithm using random subsampling to compute patient-specific confidence intervals for network localizations. Our findings highlight the difference in robustness between commonly used network metrics and provide tools to assess confidence in intracranial network localization. We present these techniques as an important step toward translating personalized network models of seizures into rigorous, quantitative approaches to invasive therapy., (© 2020 Massachusetts Institute of Technology.)

Patients with drug-resistant epilepsy often require surgery to become seizure-free. While laser ablation and implantable stimulation devices have lowered the morbidity of these procedures, seizure-free rates have not dramatically improved, particularly for patients without focal lesions. This is in part because it is often unclear where to intervene in these cases. To address this clinical need, several research groups have published methods to map epileptic networks but applying them to improve patient care remains a challenge. In this study we advance clinical translation of these methods by: (i) presenting and sharing a robust pipeline to rigorously quantify the boundaries of the resection zone and determining which intracranial EEG electrodes lie within it; (ii) validating a brain network model on a retrospective cohort of 28 patients with drug-resistant epilepsy implanted with intracranial electrodes prior to surgical resection; and (iii) sharing all neuroimaging, annotated electrophysiology, and clinical metadata to facilitate future collaboration. Our network methods accurately forecast whether patients are likely to benefit from surgical intervention based on synchronizability of intracranial EEG (area under the receiver operating characteristic curve of 0.89) and provide novel information that traditional electrographic features do not. We further report that removing synchronizing brain regions is associated with improved clinical outcome, and postulate that sparing desynchronizing regions may further be beneficial. Our findings suggest that data-driven network-based methods can identify patients likely to benefit from resective or ablative therapy, and perhaps prevent invasive interventions in those unlikely to do so., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Patients with poorly controlled seizures are at elevated risk of epilepsy-related morbidity and mortality. For patients with drug-resistant epilepsy that is focal at onset, epilepsy surgery is the most effective treatment available and offers a 50-80% cure rate. Yet, it is estimated that only 1% of patients with drug-resistant epilepsy undergo surgery in a timely fashion, and delays to surgery completion are considerable. The aim of this study was to increase availability and decrease delay of surgical evaluation at our epilepsy center for patients with drug-resistant epilepsy by removing process barriers., Methods: For this quality improvement (QI) initiative, we convened a multidisciplinary team to construct a presurgical pathway process map and complete root cause analysis. This inquiry revealed that the current condition allowed patients to proceed through the pathway without centralized oversight. Therefore, we appointed an epilepsy surgery nurse manager, and under her direction, multiple additional process improvement interventions were applied. We then retrospectively compared preintervention (2014-2015) and postintervention (2016-2017) cohorts of patient undergoing the presurgical pathway. The improvement measures were patient throughput and pathway sojourn times. As a balancing measure, we considered the proportion of potentially eligible patients (epilepsy monitoring unit (EMU) admissions) who ultimately completed epilepsy surgery., Results: Following our intervention, patient throughput was substantially increased for each stage of the presurgical pathway (32%-96% growth). However, patient sojourn times were not improved overall. No difference was observed in the proportion of possible candidates who ultimately completed epilepsy surgery., Significance: Although process improvement expanded the number of patients who underwent epilepsy surgical evaluation, we experienced concurrent prolongation of the time from pathway initiation to completion. Ongoing improvement cycles will focus on newly identified residual sources of bottleneck and delay., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The diagnostic distinction between epilepsy and psychogenic nonepileptic seizures (PNES) can be challenging. Previous studies have demonstrated that experts in conversation analysis can identify linguistic and interactional features in transcripts and recordings of interviews with patients that reliably distinguish between epilepsy and PNES. In this study, ten senior neurology trainees took part in a one-day intervention workshop about linguistic and interactional differences in the conversation behavior of patients with epilepsy and those with PNES. Participants were familiarized with a 12-item questionnaire designed to capture their conversational observations immediately after talking to a patient with seizures. After the intervention, 55 initial outpatient visits of patients referred to seizure clinics were video and audio recorded. All medical diagnoses were confirmed two years after initial presentation on the basis of a chart review (including MRI and EEG findings) by a fully trained epilepsy expert. Postvisit questionnaires relating to patients confirmed to have epilepsy (n=20) or PNES (n=13) were analyzed. Doctors' mean responses to 6 of the 12 questions about linguistic and interactional observations differed significantly between the groups with epilepsy and PNES. Receiver operating curve analysis showed that a summation scale based on items demonstrating significant between-group differences correctly classified 81.8% of patients as having epilepsy or PNES. This study shows that a brief Conversation Analytic teaching intervention can enable neurologists to identify linguistic and interactional features supporting the differentiation of epilepsy and PNES as they take their patients' history in routine seizure clinic consultations, potentially improving diagnostic accuracy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Question design during history-taking has clear implications for patients' ability to share their concerns in general and their seizure experiences in particular. Studies have shown that unusually open questions at the start of the consultation enable patients to display interactional and linguistic markers which may help with the otherwise challenging differentiation of epileptic from nonepileptic seizures (NES). In this study, we compared the problem presentation approach taken by trainee neurologists in outpatient encounters with new patients before and after a one-day conversation analytic training intervention in which doctors were taught to adopt an open format of question design and recognize diagnostically relevant linguistic features. We audio/video-recorded clinical encounters between ten doctors, their patients, and accompanying persons; transcribed the interactions; and carried out quantitative and qualitative analyses. We studied 39 encounters before and 55 after the intervention. Following the intervention, doctors were significantly more likely to use nondirective approaches to soliciting patient accounts of their presenting complaints that invited the patient to describe their problems from their own point of view and gave them better opportunity to determine the initial agenda of the encounter. The time to first interruption by the doctor increased (from 52 to 116 s, p<.001). While patients were given more time to describe their seizure experiences, the overall appointment length did not increase significantly (19 vs 21 min, n.s.). These changes gave patients more conversational space to express their concerns and, potentially, to demonstrate the interactional and linguistic features previously found to help differentiate between epilepsy and NES, without impacting the length of the consultations., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Burst suppression (BS) is an electroencephalogram (EEG) pattern that is characterized by brief bursts of spikes, sharp waves, or slow waves of relatively high amplitude alternating with periods of relatively flat EEG or isoelectric periods. The pattern is usually associated with coma, severe encephalopathy of various etiologies, or general anesthesia. We describe an unusual case of anoxic brain injury in which a BS pattern was seen during behaviorally defined sleep during a routine outpatient EEG study.

Niemann-Pick disease refers to a group of autosomal recessive lipid storage disorders associated with a variable degree of neurological manifestations in addition to other organ involvement. Niemann-Pick disease is divided into types A-C. Of interest to neurologists is Niemann-Pick type C because of the association with neurological manifestations that are not confined to childhood. The clinical presentation of Niemann-Pick type C is variable, depending on age at onset. Neurological symptoms vary with age: hypotonia, delay in developmental motor milestones, falls, seizures, learning difficulties, ataxia with cognitive deficits and psychosis. The definitive diagnosis of Niemann-Pick type C requires demonstration of abnormal intracellular cholesterol trafficking using the filipin test. Therapeutic interventions are few but one that is of interest is miglustat, which has been approved for specific treatment of the neurological manifestations. It showed improvement in horizontal saccadic eye movement and a trend towards improvement or stabilisation in swallowing, hearing and walking. Niemann-Pick type C should be considered in patients with early-onset ataxia associated with progressive learning/cognitive difficulties even in the absence of vertical gaze palsy.

Spasticity is common in many neurological disorders, such as stroke and multiple sclerosis. It is part of the upper motor neurone syndrome manifesting as increased tone, clonus, spasms, spastic dystonia and co-contractions. The impact of spasticity varies from it being a subtle neurological sign to severe spasticity causing pain and contractures. Existing spasticity can be worsened by external factors such as constipation, urinary tract infections or pressure ulcers. Its management involves identification and elimination of triggers; neurophysiotherapy; oral medications such as baclofen, tizanidine and dantrolene; focal injection of botulinum toxin, alcohol or phenol, or baclofen delivered intrathecally through a pump; and surgical resection of selected dorsal roots of the spinal cord. This article reviews the current understanding of pathophysiology, clinical features and management of spasticity.