A brain atlas of axonal and synaptic delays based on modelling of cortico-cortical evoked potentials.

Epilepsy presurgical investigation may include focal intracortical single-pulse electrical stimulations with depth electrodes, which induce cortico-cortical evoked potentials at distant sites because of white matter connectivity. Cortico-cortical evoked potentials provide a unique window on functional brain networks because they contain sufficient information to infer dynamical properties of large-scale brain connectivity, such as preferred directionality and propagation latencies. Here, we developed a biologically informed modelling approach to estimate the neural physiological parameters of brain functional networks from the cortico-cortical evoked potentials recorded in a large multicentric database. Specifically, we considered each cortico-cortical evoked potential as the output of a transient stimulus entering the stimulated region, which directly propagated to the recording region. Both regions were modelled as coupled neural mass models, the parameters of which were estimated from the first cortico-cortical evoked potential component, occurring before 80 ms, using dynamic causal modelling and Bayesian model inversion. This methodology was applied to the data of 780 patients with epilepsy from the F-TRACT database, providing a total of 34 354 bipolar stimulations and 774 445 cortico-cortical evoked potentials. The cortical mapping of the local excitatory and inhibitory synaptic time constants and of the axonal conduction delays between cortical regions was obtained at the population level using anatomy-based averaging procedures, based on the Lausanne2008 and the HCP-MMP1 parcellation schemes, containing 130 and 360 parcels, respectively. To rule out brain maturation effects, a separate analysis was performed for older (>15 years) and younger patients (<15 years). In the group of older subjects, we found that the cortico-cortical axonal conduction delays between parcels were globally short (median = 10.2 ms) and only 16% were larger than 20 ms. This was associated to a median velocity of 3.9 m/s. Although a general lengthening of these delays with the distance between the stimulating and recording contacts was observed across the cortex, some regions were less affected by this rule, such as the insula for which almost all efferent and afferent connections were faster than 10 ms. Synaptic time constants were found to be shorter in the sensorimotor, medial occipital and latero-temporal regions, than in other cortical areas. Finally, we found that axonal conduction delays were significantly larger in the group of subjects younger than 15 years, which corroborates that brain maturation increases the speed of brain dynamics. To our knowledge, this study is the first to provide a local estimation of axonal conduction delays and synaptic time constants across the whole human cortex in vivo, based on intracerebral electrophysiological recordings.

Predictors of hyperkinetic seizures.

OBJECTIVE: To identify predisposing factors for hyperkinetic seizure occurrence in a representative cohort of surgically treated patients with drug-resistant focal epilepsy. METHODS: We retrospectively recruited all seizure-free patients after epilepsy surgery with a postoperative follow-up ≥12 months. Patients were classified as presenting with hyperkinetic seizures if at least 2 episodes occurred during their disease history, based on clear-cut anamnestic description and/or video-EEG/stereo-EEG recordings. We performed univariable and multivariable logistic regression models to study the association between the occurrence of hyperkinetic seizures and some predictors. RESULTS: From a pool of 1758 consecutive patients who underwent surgery from 1996 to 2017, we identified 974 seizure-free cases. Considering at least 1-year follow-up, 937 cases were included (511 males, 91 patients with hyperkinetic seizures). Variables significantly associated with an increased risk of hyperkinetic seizure occurrence were (1) presence of epilepsy with sleep-related seizures (SRE) (P < 0.001); (2) histological diagnosis of type II focal cortical dysplasia (FCD) (P < 0.001); (3) resection including the frontal lobe (P = 0.002) (4) duration of epilepsy at surgery (P < 0.001) and (5) high seizure frequency at surgery (weekly: P = 0.02 - daily: P = 0.05). A resection including the occipital lobe reduced the risk of hyperkinetic seizures (P = 0.05). About 63% of patients had hyperkinetic seizure onset before 12 years and it was rarely reported before 5 years of age. SIGNIFICANCE: Our findings underlie the role of SRE, type II FCD and frontal epileptogenic zone as predictors of hyperkinetic seizure occurrence and highlight an age-dependent effect in favoring hyperkinetic manifestations.

Intracranial recordings in humans reveal specific hippocampal spectral and dorsal vs. ventral connectivity signatures during visual, attention and memory tasks.

Invasive brain recordings using many electrodes across a wide range of tasks provide a unique opportunity to study the role of oscillatory patterning and functional connectivity. We used large-scale recordings (stereo EEG) within and beyond the human hippocampus to investigate the role of distinct frequency oscillations during real-time execution of visual, attention and memory tasks in eight epileptic patients. We found that activity patterns in the hippocampus showed task and frequency dependent properties. Importantly, we found distinct connectivity signatures, in particular concerning parietal-hippocampal connectivity, thus revealing large scale synchronization of networks involved in memory tasks. Comparing the power per frequency band, across tasks and hippocampal regions (anterior/posterior) we confirmed a main effect of frequency band (p = 0.002). Gamma band activity was higher for visuo-spatial memory tasks in the anterior hippocampus. Further, we found that alpha and beta band activity in posterior hippocampus had larger modulation for high memory load visual tasks (p = 0.004). Three functional connectivity task related networks were identified: (dorsal) parietal-hippocampus (visual attention and memory), ventral stream- hippocampus and hippocampal-frontal connections (mainly tasks involving face recognition or object based search). These findings support the critical role of oscillatory patterning in the hippocampus during visual and memory tasks and suggests the presence of task related spectral and functional connectivity signatures. These results show that the use of large scale human intracranial recordings can validate the role of oscillatory and functional connectivity patterns across a broad range of cognitive domains.

Association Between Semiology and Anatomo-functional Localization in Patients With Cingulate Epilepsy: A Cohort Study.

BACKGROUND AND OBJECTIVES: Cingulate epilepsy (CE) is a rare type of focal epilepsy that is challenging to diagnose because of the polymorphic semiology of the seizures, mimicking other types of epilepsy, and the limited utility of scalp EEG. METHODS: We selected consecutive patients with drug-resistant CE who were seizure-free after surgery, with seizure onset zone (SOZ) confirmed in the cingulate cortex (CC) by histology or stereo EEG. We analyzed subjective and objective ictal manifestations using video recordings and correlated semiology with anatomical CC subregion (anterior, anterior middle, posterior middle, and posterior) localization of SOZ. RESULTS: We analyzed 122 seizures in 57 patients. Seizures were globally characterized by complex behaviors, typically natural seeming and often accompanied by emotional components. All objective ictal variables considered (pronation of the body or arising from a lying/sitting position, tonic/dystonic posturing, hand movements, asymmetry, vocalizations, fluidity and repetitiveness of motor manifestations, awareness, and emotional and autonomic components) were differently distributed among CC subregions (p < 0.05). Along the rostro-caudal axis, fluidity and repetitiveness of movement, vocalizations, body pronation, and emotional components decreased anterior-posteriorly, whereas tonic/dystonic postures, signs of lateralization, and awareness increased. Vestibular and asymmetric somatosensory, somatosensory, and epigastric and enteroceptive/autonomic symptoms were distributed differently among CC subregions (p < 0.05). Along the rostro-caudal axis, vestibular, somatosensory, and somatosensory asymmetric symptoms increased anterior-posteriorly. DISCUSSION: CE is characterized by a spectrum of semiologic manifestations with a topographic distribution. CE semiology could indicate which cingulate sector is primarily involved.

Investigating visuo-spatial neglect and visual extinction during intracranial electrical stimulations: The role of the right inferior parietal cortex.

Both visuo-spatial neglect and visual extinction may occur following right-brain damage. So far, studies on brain-damaged patients have not provided definite evidence about which lesion patterns may lead to the association or dissociation of these deficits. This study was set out to address this issue using Intracranial Electrical Stimulation (IES) in a group of nine patients affected by refractory epilepsy. Cerebral regions associated with visuo-spatial neglect and visual extinction were stimulated, including the right frontal, temporal, and posterior parietal areas. During IES, patients with intracranial implantation involving at least one of these cortical regions were administered with a manual line bisection task (N = 9) to assess visuo-spatial neglect, and a computerized task (N = 8) assessing visual extinction. Results showed that parietal IES induced a rightward bias at the manual bisection task, together with a general improvement in reaction times at bilateral and unilateral visual stimuli detection at the extinction task. The occurrence of visual extinction did not vary across stimulations. By adopting a complementary approach to anatomo-clinical correlation studies, our work corroborates the notion that lesions to the right inferior parietal lobule play a pivotal role in the pathogenesis of visuo-spatial neglect. Importantly, our results also suggest that temporarily interfering with the activity of this region is not sufficient per se to generate visual extinction, which instead may involve a broader and/or different network, possibly extending beyond the cerebral regions considered here, posing important theoretical and clinical implications.

Low-grade tumour over the left temporal neocortex and ictal asystole: network and surgical implications.

We describe a patient with focal epilepsy characterized by ictal asystole episodes and low-grade tumour over the left temporal neocortex. Non-invasive pre-surgical evaluation showed an epileptogenic zone extended beyond the low-grade tumour. This extension was confirmed by intraoperative electrocorticography. One-stage surgery with anterior temporal lobe resection was performed. The patient was seizure-free after one year of follow-up. Detailed electroclinical and therapeutic reasoning with hypotheses defining epileptogenic and symptomatogenic networks are discussed.

Intracerebral electrical stimulations of the temporal lobe: A stereoelectroencephalography study.

The functional anatomy of the anteromesial portion of the temporal lobe and its involvement in epilepsy can be explored by means of intracerebral electrical stimulations. Here, we aimed to expand the knowledge of its physiological and pathophysiological symptoms by conducting the first large-sample systematic analysis of 1529 electrical stimulations of this anatomical region. We retrospectively analysed all clinical manifestations induced by intracerebral electrical stimulations in 173 patients with drug-resistant focal epilepsy with at least one electrode implanted in this area. We found that high-frequency stimulations were more likely to evoke electroclinical manifestations (p < .0001) and also provoked 'false positive' seizures. Multimodal symptoms were associated with EEG electrical modification (after discharge) (p < .0001). Visual symptoms were not associated with after discharge (p = .0002) and were mainly evoked by stimulation of the hippocampus (p = .009) and of the parahippocampal gyrus (p = .0212). 'False positive seizures' can be evoked by stimulation of the hippocampus, parahippocampal gyrus and amygdala, likely due to their intrinsic low epileptogenic threshold. Visual symptoms evoked in the hippocampus and parahippocampal gyrus, without EEG changes, are physiological symptoms and suggest involvement of these areas in the visual ventral stream. Our findings provide meaningful guidance in the interpretation of intracranial EEG studies of the temporal lobe.

Temporal lobe epilepsy: A never-ending story.

INTRODUCTION: Semiology and anatomo-electroclinical correlations remain invaluable for maintaining the level of excellence in temporal lobe epilepsy (TLE) surgery, in parallel to the constantly evolving technical progress. The aim of this study was to address semiological frequent and not so frequent signs, rarities and red flags in a long follow-up surgical series of patients suffering from TLE. METHODS: Patients operated within the boundaries of the TL at our center, with presurgical video-EEG recorded seizures and seizure free after a postoperative follow-up of at least 24 months were included. Ictal semiology was systematically described and new red flags were explored by comparing with a second group of patients with the same inclusion criteria but whose outcome had been unfavorable (Engel II-IV). RESULTS: Sixty-two patients were included, 46 seizure free and 16 with outcome Engel II-IV. Most seizure-free patients had a classical semiological presentation including aura (69.6%, abdominal the most frequent), followed by loss of responsiveness (90.2%) oral automatisms (90.7%), ipsilateral gestural automatisms (53.5%), contralateral upper limb dystonia (37.5%) or immobility (39.1%), and early ipsilateral non-versive head orientation (33.3%). More infrequent presentations were also present in the group of seizure-free patients: ictal language disturbance (13%), maintenance of responsiveness during seizures (9.8%), and contralateral rhythmic non manipulative automatism (6.9%). The presence of an isolated viscerosensory and/or psychic aura was significantly more frequent in the seizure-free group (p = 0.017), as well as oroalimentary automatisms (p = 0.005). Two signs were only present in the group with outcome Engel II-IV, constituting possible red flags (0.06 < p < 0.07): inferior limbs stepping-like automatisms and postictal dysarthria. CONCLUSION: An adequate clinical exam during seizures and a careful analysis of video recordings allow to recognize infrequent but well-characterized ictal signs that are part of the range of semiology in TLE, together with the most frequent and classical ictal presentations. Special attention to the localization hypothesis must be paid in the absence of oroalimentary automatisms or when the signs classified as possible red flags emerge.

SEEG re-exploration in a patient with complex frontal epilepsy with rapid perisylvian propagation and mixed "startle - reflex" seizures.

The SEEG International Course, organised in 2017, focused on the investigation and surgery of insulo-perisylvian epilepsies. We present one representative complex case that was discussed. The patient had seizures displaying startle/reflex components. He was MRI negative, while other non-invasive investigations offered only partially concordant data. Initial SEEG exploration resulted in an incomplete definition of the epileptogenic zone. A second SEEG followed, which led to a thorough assessment of the seizure onset zone and the epileptic network, localised to the lateral inferior premotor cortex, explaining the incongruent data obtained beforehand. This was the basis of a tailored resection with a favourable outcome. The patient has been seizure-free for five years without any motor nor cognitive deficits, but with pharmacodependence to one AED. The electroclinical reasoning is presented, accompanied by relevant commentaries and recommendations from the tutors [Published with video sequences].

Electrical stimulation for seizure induction during SEEG exploration: a useful predictor of postoperative seizure recurrence?

OBJECTIVE: Direct electrical stimulations of cerebral cortex are a traditional part of stereoelectroencephalography (SEEG) practice, but their value as a predictive factor for seizure outcome has never been carefully investigated. PATIENTS AND METHOD: We retrospectively analysed a cohort of 346 patients operated on for drug-resistant focal epilepsy after SEEG exploration. As potential predictors we included: aetiology, MRI data, age of onset, duration of epilepsy, age at surgery, topography of surgery and whether a seizure was induced by either low frequency electrical stimulation (LFS) or high frequency electrical stimulation. RESULTS: Of 346 patients, 63.6% had good outcome (no seizure recurrence, Engel I). Univariate analysis demonstrated significant correlation with favourable outcome (Engel I) for: aetiology, positive MRI and seizure induced by stimulation. At multivariate analysis, informative MRI, type II focal cortical dysplasia and tumour reduced the risk of seizure recurrence (SR) by 47%, 58% and 81%, respectively. Compared with the absence of induced seizures, the occurrence of ictal events after LFS significantly predicts a favourable outcome on seizures, with only 44% chance of disabling SR at last follow-up. CONCLUSION: Among the already known predictors outcome, seizure induction by LFS therefore represents a positive predictive factor for seizure outcome after surgery.

Could the 2017 ILAE and the four-dimensional epilepsy classifications be merged to a new "Integrated Epilepsy Classification"?

Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the "Four-dimensional epilepsy classification" (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years. The extensive arguments for and against these two classification systems made in the past have mainly focused on the shortcomings of each system, presuming that they are incompatible. As a further more detailed discussion of the differences seemed relatively unproductive, we here review and assess the concordance between these two approaches that has evolved over time, to consider whether a classification incorporating the best aspects of the two approaches is feasible. To facilitate further discussion in this direction we outline a concrete proposal showing how such a compromise could be accomplished, the "Integrated Epilepsy Classification". This consists of five categories derived to different degrees from both of the classification systems: 1) a "Headline" summarizing localization and etiology for the less specialized users, 2) "Seizure type(s)", 3) "Epilepsy type" (focal, generalized or unknown allowing to add the epilepsy syndrome if available), 4) "Etiology", and 5) "Comorbidities & patient preferences".

Trends in pediatric epilepsy surgery in Europe between 2008 and 2015: Country-, center-, and age-specific variation.

OBJECTIVE: To profile European trends in pediatric epilepsy surgery (<16 years of age) between 2008 and 2015. METHODS: We collected information on volumes and types of surgery, pathology, and seizure outcome from 20 recognized epilepsy surgery reference centers in 10 European countries. RESULTS: We analyzed retrospective aggregate data on 1859 operations. The proportion of surgeries significantly increased over time (P < .0001). Engel class I outcome was achieved in 69.3% of children, with no significant improvement between 2008 and 2015. The proportion of histopathological findings consistent with glial scars significantly increased between the ages of 7 and 16 years (P for trend = .0033), whereas that of the remaining pathologies did not vary across ages. A significant increase in unilobar extratemporal surgeries (P for trend = .0047) and a significant decrease in unilobar temporal surgeries (P for trend = .0030) were observed between 2008 and 2015. Conversely, the proportion of multilobar surgeries and unrevealing magnetic resonance imaging cases remained unchanged. Invasive investigations significantly increased, especially stereo-electroencephalography. We found different trends comparing centers starting their activity in the 1990s to those whose programs were developed in the past decade. Multivariate analysis revealed a significant variability of the proportion of the different pathologies and surgical approaches across countries, centers, and age groups between 2008 and 2015. SIGNIFICANCE: Between 2008 and 2015, we observed a significant increase in the volume of pediatric epilepsy surgeries, stability in the proportion of Engel class I outcomes, and a modest increment in complexity of the procedures.

Stereo-EEG ictal/interictal patterns and underlying pathologies.

PURPOSE: To define Stereo-EEG (SEEG) ictal and interictal patterns associated with different pathologies in a cohort of patients with drug-resistant focal epilepsy. METHODS: We retrospectively analyzed findings from 102 patient with epilepsy due to Polymicrogyria (PMG), Periventricular Nodular Heterotopia (PNH), Focal Cortical Dysplasia (FCD) type I, IIa, IIb and Hippocampal Sclerosis (HS). Ictal and interictal SEEG recordings were reviewed to describe Seizure Onset Zone (SEEG-SOZ) patterns and to define the Lesional and Irritative Zones. RESULTS: Five SEEG-SOZ patterns were identified: significant associations were found between low-voltage fast activity and PMG and between repetitive fast spikes bursts and FCD type IIa. A trend was found between fast activity and PNH, rhythmic sharp activity and FCD type I, repetitive fast spikes bursts and FCD type IIb, slow burst and HS. In 62 of the 102 patients, a complete surgical resection of the SEEG-SOZ was performed, and in 12 patients a partial resection was carried out to preserve eloquent areas. In 18 patients (15 with PNH) the SEEG-SOZ was thermo-coagulated. Seizure freedom was achieved in 58% of surgically treated patients and in 72% of those treated with thermocoagulation (mean ±â€¯SD follow-up 5.9 ±â€¯2.3 years). Seizure freedom after surgery was achieved in 84% of the patients with PMG, FCD I, IIa and IIb presenting with characteristic SEEG-SOZ patterns. With the exception of FCD type II, interictal activity was not sufficient to identify SEEG-SOZ boundaries. CONCLUSION: The study demonstrates that specific histopathologies correlate with particular neurophysiological patterns, reflecting lesion-specific seizure patterns in focal epilepsies.

Stereoelectroencephalography: retrospective analysis of 742 procedures in a single centre.

This retrospective description of a surgical series is aimed at reporting on indications, methodology, results on seizures, outcome predictors and complications from a 20-year stereoelectroencephalography (SEEG) activity performed at a single epilepsy surgery centre. Prospectively collected data from a consecutive series of 742 SEEG procedures carried out on 713 patients were reviewed and described. Long-term seizure outcome of SEEG-guided resections was defined as a binomial variable: absence (ILAE classes 1-2) or recurrence (ILAE classes 3-6) of disabling seizures. Predictors of seizure outcome were analysed by preliminary uni/bivariate analyses followed by multivariate logistic regression. Furthermore, results on seizures of these subjects were compared with those obtained in 1128 patients operated on after only non-invasive evaluation. Survival analyses were also carried out, limited to patients with a minimum follow-up of 10 years. Resective surgery has been indicated for 570 patients (79.9%). Two-hundred and seventy-nine of 470 patients operated on (59.4%) were free of disabling seizures at least 2 years after resective surgery. Negative magnetic resonance and post-surgical lesion remnant were significant risk factors for seizure recurrence, while type II focal cortical dysplasia, balloon cells, glioneuronal tumours, hippocampal sclerosis, older age at epilepsy onset and periventricular nodular heterotopy were significantly associated with seizure freedom. Twenty-five of 153 patients who underwent radio-frequency thermal coagulation (16.3%) were optimal responders. Thirteen of 742 (1.8%) procedures were complicated by unexpected events, including three (0.4%) major complications and one fatality (0.1%). In conclusion, SEEG is a safe and efficient methodology for invasive definition of the epileptogenic zone in the most challenging patients. Despite the progressive increase of MRI-negative cases, the proportion of seizure-free patients did not decrease throughout the years.

Critique of the 2017 epileptic seizure and epilepsy classifications.

This article critiques the International League Against Epilepsy (ILAE) 2015-2017 classifications of epilepsy, epileptic seizures, and status epilepticus. It points out the following shortcomings of the ILAE classifications: (1) they mix semiological terms with epileptogenic zone terminology; (2) simple and widely accepted terminology has been replaced by complex terminology containing less information; (3) seizure evolution cannot be described in any detail; (4) in the four-level epilepsy classification, level two (epilepsy category) overlaps almost 100% with diagnostic level one (seizure type); and (5) the design of different classifications with distinct frameworks for newborns, adults, and patients in status epilepticus is confusing. The authors stress the importance of validating the new ILAE classifications and feel that the decision of Epilepsia to accept only manuscripts that use the ILAE classifications is premature and regrettable.

Clinical features of sleep-related hypermotor epilepsy in relation to the seizure-onset zone: A review of 135 surgically treated cases.

OBJECTIVES: Sleep-related hypermotor epilepsy (SHE), formerly nocturnal frontal lobe epilepsy, is characterized by abrupt and typically sleep-related seizures with motor patterns of variable complexity and duration. They seizures arise more frequently in the frontal lobe than in the extrafrontal regions but identifying the seizure onset-zone (SOZ) may be challenging. In this study, we aimed to describe the clinical features of both frontal and extrafrontal SHE, focusing on ictal semiologic patterns in order to increase diagnostic accuracy. METHODS: We retrospectively analyzed the clinical features of patients with drug-resistant SHE seen in our center for epilepsy surgery. Patients were divided into frontal and extrafrontal SHE (temporal, operculoinsular, and posterior SHE). We classified seizure semiology according to four semiology patterns (SPs): elementary motor signs (SP1), unnatural hypermotor movements (SP2), integrated hypermotor movements (SP3), and gestural behaviors with high emotional content (SP4). Early nonmotor manifestations were also assessed. RESULTS: Our case series consisted of 91 frontal SHE and 44 extrafrontal SHE cases. Frontal and extrafrontal SHE shared many features such as young age at onset, high seizure-frequency rate, high rate of scalp electroencephalography (EEG) and magnetic resonance imaging (MRI) abnormalities, similar histopathologic substrates, and good postsurgical outcome. Within the frontal lobe, SPs were organized in a posteroanterior gradient (SP1-4) with respect to the SOZ. In temporal SHE, SP1 was rare and SP3-4 frequent, whereas in operculoinsular and posterior SHE, SP4 was absent. Nonmotor manifestations were frequent (70%) and some could provide valuable localizing information. SIGNIFICANCE: Our study shows that the presence of certain SP and nonmotor manifestations may provide helpful information to localize seizure onset in patients with SHE.

Classification of paroxysmal events and the four-dimensional epilepsy classification system.

This educational review describes the classification of paroxysmal events and a four-dimensional epilepsy classification system. Paroxysmal events are classified as epileptic and non-epileptic paroxysmal events. Non-epileptic events are, in turn, classified as psychogenic and organic paroxysmal events. The following four dimensions are used to classify epileptic paroxysmal events: ictal semiology, the epileptogenic zone, etiology, and comorbidities. Efforts are made to keep these four dimensions as independent as possible. The review also includes 12 educational vignettes and three more detailed case reports classified using the 2017 classification of the ILAE and the four-dimensional epilepsy classification. In addition, a case is described which is classified using the four-dimensional epilepsy classification with different degrees of precision by an emergency department physician, a neurologist, and an epileptologist. [Published with video sequences on www.epilepticdisorders.com].

Seizure duration and latency of hypermotor manifestations distinguish frontal from extrafrontal onset in sleep-related hypermotor epilepsy.

Sleep-related hypermotor epilepsy (SHE) is an epilepsy syndrome that is characterized by the occurrence of sleep-related hypermotor seizures of variable complexity and duration. Seizures usually arise in the frontal lobe, but extrafrontal seizure onset zones are well described. To identify clinically relevant ictal features of SHE that could distinguish a frontal from an extrafrontal onset zone, we conducted a retrospective analysis of seizure characteristics in 58 patients with drug-resistant SHE (43 frontal and 15 extrafrontal) who underwent video-stereo-electroencephalographic recordings and became seizure-free after epilepsy surgery. We found that the mean duration of electrographic seizures and clinically observable ictal manifestations were significantly shorter in frontal SHE compared to extrafrontal SHE. The mean latency between electrographic seizure onset and the onset of hypermotor manifestations was also shorter in frontal SHE. Accordingly, a latency > 5 seconds between the first video-detectable movement (eg, eye opening or a minor motor event) and the onset of hypermotor manifestations yielded a sensitivity of 75% and a specificity of 90% for an extrafrontal onset, thereby indicating that specific ictal features in SHE can provide clinically useful clues to increase diagnostic accuracy in this syndrome.