The involvement of the piriform cortex in non-lesional temporal lobe epilepsy: an uncommon component of the epileptogenic network.

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.

An ordinal clinical score predicts seizure freedom after minimally invasive epilepsy surgery.

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.

An Unusual Case of Hypothalamic Hamartoma With Nongelastic Seizures and Posterior Cortex Connectivity.

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.

Stereoelectroencephalography of the Deep Brain: Basal Ganglia and Thalami.

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.

Escaping the Procrustean Bed: A Perspective on Pediatric Stereoelectroencephalography.

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.

Selective Posterior Cerebral Artery Wada Better Predicts Good Memory and Naming Outcomes Following Selective Stereotactic Thermal Ablation for Medial Temporal Lobe Epilepsy Than Internal Carotid Artery Wada.

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.

A multi-center comparison of surgical techniques for corpus Callosotomy in pediatric drug-resistant epilepsy.

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.

Intracranial investigation of piriform cortex epilepsy during odor presentation.

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.

Mapping the Central Sulcus Extraoperatively Using Stereoelectroencephalography: A New Application of an Established Method.

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.

Epilepsy surgery in children with genetic etiologies: A prospective evaluation of current practices and outcomes.

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.

Education Research: Quality and Validity Evidence for a National In-Training Examination for Epilepsy Fellows.

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.

Interventions for ADHD in children & adolescents with epilepsy: A review and decision tree to guide clinicians.

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.

The Referential Montage Inadequately Localizes Corticocortical Evoked Potentials in Stereoelectroencephalography.

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.

Subjective distinguishability of seizure and non-seizure Déjà Vu: A case report, brief literature review, and research prospects.

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.

Electroencephalography characteristics to predict one-year outcomes in pediatric anti-NMDA receptor encephalitis.

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.

Cognitive and Emotional Mapping With SEEG.

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.

Developing and Implementing a Standardized Ictal Examination in the Epilepsy Monitoring Unit.

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.

The precuneal cortex: anatomy and seizure semiology.

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.

Neurovascular networks in epilepsy: Correlating ictal blood perfusion with intracranial electrophysiology.

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.