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.

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.

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.

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.

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.

Motor and emotional behaviours elicited by electrical stimulation of the human cingulate cortex.

The cingulate cortex is a mosaic of different anatomical fields, whose functional characterization is still a matter of debate. In humans, one method that may provide useful insights on the role of the different cingulate regions, and to tackle the issue of the functional differences between its anterior, middle and posterior subsectors, is intracortical electrical stimulation. While previous reports showed that a variety of integrated behaviours could be elicited by stimulating the midcingulate cortex, little is known about the effects of the electrical stimulation of anterior and posterior cingulate regions. Moreover, the internal arrangement of different behaviours within the midcingulate cortex is still unknown. In the present study, we extended previous stimulation studies by retrospectively analysing all the clinical manifestations induced by intracerebral high frequency electrical stimulation (50 Hz, pulse width: 1 ms, 5 s, current intensity: average intensity of 2.7 ± 0.7 mA, biphasic) of the entire cingulate cortex in a cohort of 329 drug-resistant epileptic patients (1789 stimulation sites) undergoing stereo-electroencephalography for a presurgical evaluation. The large number of patients, on one hand, and the accurate multimodal image-based localization of stereo-electroencephalography electrodes, on the other hand, allowed us to assign specific functional properties to modern anatomical subdivisions of the cingulate cortex. Behavioural or subjective responses were elicited from the 32.3% of all cingulate sites, mainly located in the pregenual and midcingulate regions. We found clear functional differences between the pregenual part of the cingulate cortex, hosting the majority of emotional, interoceptive and autonomic responses, and the anterior midcingulate sector, controlling the majority of all complex motor behaviours. Particularly interesting was the 'actotopic' organization of the anterior midcingulate sector, arranged along the ventro-dorsal axis: (i) whole-body behaviours directed to the extra-personal space, such as getting-up impulses, were elicited ventrally, close to the corpus callosum; (ii) hand actions in the peripersonal space were evoked by the stimulation of the intermediate position; and (iii) body-directed actions were induced by the stimulation of the dorsal branch of the cingulate sulcus. The caudal part of the midcingulate cortex and the posterior cingulate cortex were, in contrast, poorly excitable, and mainly devoted to sensory modalities. In particular, the caudal part of the midcingulate cortex hosted the majority of vestibular responses, while posterior cingulate cortex was the principal recipient of visual effects. We will discuss our data in the light of current controversies on the role of the cingulate cortex in cognition and emotion.

Four-dimensional maps of the human somatosensory system.

A fine-grained description of the spatiotemporal dynamics of human brain activity is a major goal of neuroscientific research. Limitations in spatial and temporal resolution of available noninvasive recording and imaging techniques have hindered so far the acquisition of precise, comprehensive four-dimensional maps of human neural activity. The present study combines anatomical and functional data from intracerebral recordings of nearly 100 patients, to generate highly resolved four-dimensional maps of human cortical processing of nonpainful somatosensory stimuli. These maps indicate that the human somatosensory system devoted to the hand encompasses a widespread network covering more than 10% of the cortical surface of both hemispheres. This network includes phasic components, centered on primary somatosensory cortex and neighboring motor, premotor, and inferior parietal regions, and tonic components, centered on opercular and insular areas, and involving human parietal rostroventral area and ventral medial-superior-temporal area. The technique described opens new avenues for investigating the neural basis of all levels of cortical processing in humans.

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.

Ictal signs in tuberous sclerosis complex: Clinical and video-EEG features in a large series of recorded seizures.

Epilepsy is the most common neurological symptom in tuberous sclerosis complex (TSC), occurring in 72-85% of affected individuals. Despite the large number of patients reported, their electroclinical phenotype has been rarely described. We analyzed seizure semiology through ictal video-electroencephalography (V-EEG) recordings in a large series of patients. In this multicenter study, we reviewed V-EEGs of 51 patients: ictal recordings were analyzed in correlation with their clinical variables. The median age of epilepsy onset was six months (one day-16 years), with onset in the first year of life in 71% patients (36/51), in 10 of them during the neonatal period. Sixty-five percent of patients (33/51) experienced epileptic spasms in their life, with late-onset (>two years) in five; 42% of the epileptic spasms persisted after age two years, despite the onset in the first year of life. We identified four different electroclinical subsets: focal epilepsy (35%, 18/51), Lennox-Gastaut Syndrome evolution (27%, 14/51), focal seizures with persisting spasms (33%, 17/51), and spasms only (4%, 2/51). We reviewed 45 focal seizures, 13 clusters of epileptic spasms, and seven generalized seizures. In 12 patients, we recorded different seizure types. In 71% of the focal seizures (32/45), the ictal pattern was focal without diffusion. In 38% of the patients (5/13) epileptic spasms were related to typical diffuse slow wave pattern associated with superimposed fast activity, with focal predominance. Focal seizures and focal spasms resulted as the most frequent seizure types in TSC. Seizure onset was variable but showing a predominant involvement of the frontocentral regions (40%). Discrete clinical signs characterized the seizures, and behavioral arrest was the predominant first clinical objective sign. Epileptic spasms were a typical presentation at all ages, frequently asymmetrical and associated with lateralizing features, especially in older patients.

Stereo-EEG: Diagnostic and therapeutic tool for periventricular nodular heterotopia epilepsies.

OBJECTIVE: Periventricular nodular heterotopias (PNHs) are malformations of cortical development related to neuronal migration disorders, frequently associated with drug-resistant epilepsy (DRE). Stereo-electroencephalography (SEEG) is considered a very effective step of the presurgical evaluation, providing the recognition of the epileptogenic zone (EZ). At the same time, via the intracerebral electrodes it is possible to perform radiofrequency thermocoagulation (SEEG-guided RF-TC) with the aim of ablating and/or disrupting the EZ. The purpose of this study was to evaluate both the relationships between PNH and the EZ, and the efficacy of SEEG-guided RF-TC. METHODS: Twenty patients with DRE related to PNHs were studied. Inclusion criteria were the following: (1) patients with epilepsy and PNHs (unilateral or bilateral, single or multiple nodules) diagnosed on brain magnetic resonance imaging (MRI); (2) SEEG recordings available as part of the presurgical investigations, with at least one intracerebral electrode inside the heterotopia; (3) complete surgical workup with SEEG-guided RF-TC and/or with traditional neurosurgery, with a follow-up of at least 12 months. RESULTS: Complex and heterogenic epileptic networks were found in these patients. SEEG-guided RF-TC both into the nodules and/or the cortex was efficacious in the 76% of patients. Single or multiple, unilateral or bilateral PNHs are the most suitable for this procedure, whereas patients with PNHs associated with complex cortical malformations obtained excellent outcome only with traditional resective surgery. SIGNIFICANCE: Each patient had a specific epileptogenic network, independent from the number, size, or location of nodules and from the cortical malformation associated with. SEEG-guided RF-TC appears as a new and very effective diagnostic and therapeutic approach for DRE related to PNHs.

Multicenter clinical assessment of improved wearable multimodal convulsive seizure detectors.

OBJECTIVE: New devices are needed for monitoring seizures, especially those associated with sudden unexpected death in epilepsy (SUDEP). They must be unobtrusive and automated, and provide false alarm rates (FARs) bearable in everyday life. This study quantifies the performance of new multimodal wrist-worn convulsive seizure detectors. METHODS: Hand-annotated video-electroencephalographic seizure events were collected from 69 patients at six clinical sites. Three different wristbands were used to record electrodermal activity (EDA) and accelerometer (ACM) signals, obtaining 5,928 h of data, including 55 convulsive epileptic seizures (six focal tonic-clonic seizures and 49 focal to bilateral tonic-clonic seizures) from 22 patients. Recordings were analyzed offline to train and test two new machine learning classifiers and a published classifier based on EDA and ACM. Moreover, wristband data were analyzed to estimate seizure-motion duration and autonomic responses. RESULTS: The two novel classifiers consistently outperformed the previous detector. The most efficient (Classifier III) yielded sensitivity of 94.55%, and an FAR of 0.2 events/day. No nocturnal seizures were missed. Most patients had <1 false alarm every 4 days, with an FAR below their seizure frequency. When increasing the sensitivity to 100% (no missed seizures), the FAR is up to 13 times lower than with the previous detector. Furthermore, all detections occurred before the seizure ended, providing reasonable latency (median = 29.3 s, range = 14.8-151 s). Automatically estimated seizure durations were correlated with true durations, enabling reliable annotations. Finally, EDA measurements confirmed the presence of postictal autonomic dysfunction, exhibiting a significant rise in 73% of the convulsive seizures. SIGNIFICANCE: The proposed multimodal wrist-worn convulsive seizure detectors provide seizure counts that are more accurate than previous automated detectors and typical patient self-reports, while maintaining a tolerable FAR for ambulatory monitoring. Furthermore, the multimodal system provides an objective description of motor behavior and autonomic dysfunction, aimed at enriching seizure characterization, with potential utility for SUDEP warning.

Surgical treatment of polymicrogyria-related epilepsy.

OBJECTIVE: The role of resective surgery in the treatment of polymicrogyria (PMG)-related focal epilepsy is uncertain. Our aim was to retrospectively evaluate the seizure outcome in a consecutive series of patients with PMG-related epilepsy who received, or did not receive, surgical treatment, and to outline the clinical characteristics of patients who underwent surgery. METHODS: We evaluated 64 patients with epilepsy associated with magnetic resonance imaging (MRI)-documented PMG. After presurgical evaluation, 32 patients were excluded from surgical treatment and 32 were offered surgery, which was declined by 8 patients. Seizure outcome was assessed in the 40 nonsurgical and 24 surgical patients. RESULTS: Of 40 nonsurgical patients, 8 (20%) were seizure-free after a mean follow-up of 91.7 ± (standard deviation) 59.5 months. None of the eight patients who declined surgical treatment was seizure-free (mean follow-up: 74.3 ± 60.6 months). These seizure outcomes differ significantly (p = 0.000005 and p = 0.0003, respectively) from that of the 24 surgical patients, 18 of whom (66.7%) were Engel's class I postoperatively (mean follow-up: 66.5 ± 54.0 months). Of the eight patients excluded from surgery for seizure control at first visit, two had seizure recurrence at last contact. At last contact, antiepileptic drugs (AEDs) had been withdrawn in 6 of 24 surgical and in one of 40 nonsurgical cases (p = 0.0092). SIGNIFICANCE: The present study indicates that, at least in a subset of adequately selected patients with PMG-related epilepsy, surgery may provide excellent seizure outcomes. Furthermore, it suggests that surgery is superior to AEDs for achieving seizure freedom in these cases.

Multimodal responses induced by cortical stimulation of the parietal lobe: a stereo-electroencephalography study.

The functional complexity of the parietal lobe still represents a challenge for neurophysiological and functional neuroimaging studies. While the somatosensory functions of the anterior parietal cortex are well established, the posterior parietal cortex has a relevant role in processing the sensory information, including visuo-spatial perception, visual attention, visuo-motor transformations and other complex and not completely understood functions. We retrospectively analysed all the clinical manifestations induced by intracerebral bipolar electrical stimulation in 172 patients suffering from drug-resistant focal epilepsy (mean age 25.6, standard deviation 11.6; 44% females and 56% males) with at least one electrode stereotactically implanted in the parietal cortex. A total of 1186 electrical stimulations were included in the analysis, of which 88 were subsequently excluded because of eliciting pathological electric activity or inducing ictal symptomatology. In the dominant parietal lobe, clinical responses were observed for 56 (25%) of the low-frequency stimulations and for 76 (50%) of the high-frequency stimulations. In the non-dominant parietal lobe, 111 (27%) low-frequency and 176 (55%) high-frequency stimulations were associated with a clinical response. Body scheme alteration was the only clinical effect showing a lateralization, as they were evoked only in the non-dominant hemisphere. The occurrence of somatosensory sensations, motor symptoms, dysarthria and multimodal responses were significantly associated with stimulation of the postcentral gyrus (odds ratio: 5.83, P < 0.001; odds ratio: 8.77, P < 0.001; odds ratio: 5.44, P = 0.011; odds ratio: 8.33, P = 0.006; respectively). Stimulation of the intraparietal sulcus was associated with the occurrence of sensory illusions or hallucinations (odds ratio: 8.68, P < 0.001) and eyeball/eyelid movements or sensations (odds ratio: 4.35, P = 0.047). To our knowledge, this is the only currently available complete revision of electrical stimulation of the entire parietal cortex with the aim to evaluate the neurophysiology of this relevant brain region. Our analysis offers a general overview of the multiple roles of the parietal cortex and supports its crucial involvement in different networks related to complex integrative functions.media-1vid110.1093/brain/awv187_video_abstractawv187_video_abstract.

Declarative long-term memory and the mesial temporal lobe: Insights from a 5-year postsurgery follow-up study on refractory temporal lobe epilepsy.

It is largely recognized that the mesial temporal lobe and its substructure support declarative long-term memory (LTM). So far, different theories have been suggested, and the organization of declarative verbal LTM in the brain is still a matter of debate. In the current study, we retrospectively selected 151 right-handed patients with temporal lobe epilepsy with and without hippocampal sclerosis, with a homogeneous (seizure-free) clinical outcome. We analyzed verbal memory performance within a normalized scores context, by means of prose recall and word paired-associate learning tasks. Patients were tested at presurgical baseline, 6months, 2 and 5years after anteromesial temporal lobe surgery, using parallel versions of the neuropsychological tests. Our main finding revealed a key involvement of the left temporal lobe and, in particular, of the left hippocampus in prose recall rather than word paired-associate task. We also confirmed that shorter duration of epilepsy, younger age, and withdrawal of antiepileptic drugs would predict a better memory outcome. When individual memory performance was taken into account, data showed that females affected by left temporal lobe epilepsy for longer duration were more at risk of presenting a clinically pathologic LTM at 5years after surgery. Taken together, these findings shed new light on verbal declarative memory in the mesial temporal lobe and on the behavioral signature of the functional reorganization after the surgical treatment of temporal lobe epilepsy.

Epilepsy surgery in the posterior part of the brain.

Posterior cortex epilepsy surgery is rarely performed and is associated with a high number of surgical failures, partly because accurate localization of the epileptogenic zone in the posterior part of the brain is extremely difficult. We present the characteristics as well as the surgical outcome and its determinants of a cohort of 208 consecutive patients (adults/children: 125/83) operated on for drug-resistant posterior cortex epilepsy at the "Claudio Munari" Epilepsy Surgery Centre, Milan between May 1996 and May 2013 (mean postsurgical follow-up: 9.6years). In addition, we highlight the differences in anatomoelectroclinical features and outcome between (i) patients who necessitated an invasive preoperative evaluation and those who proceeded directly to surgery and (ii) adults and children. Mean age at epilepsy onset was 6.8years (91.4% with onset before 14years of age). A high seizure frequency was reported by 51% of subjects, interictal and ictal EEG features were localizing in 16% and 28% of cases, and 86% of patients had a positive, judged as more or less informative, MRI. Invasive presurgical evaluation by stereoelectroencephalography was performed in 54% of patients; explorations may schematically be grouped in three main implantation patterns. Globally, 70% of subjects achieved seizure freedom, and further, 10% achieved Engel class II, with the patients operated on in childhood achieving significantly better postsurgical results in terms of seizure freedom and drug discontinuation. Duration of epilepsy represented the most consistent predictor of surgical outcome, with early surgery being correlated with higher chances of surgical success. Therefore, we recommend an early surgical referral in cases of pharmacoresistant posterior cortex seizures. Furthermore, we suggest that surgical failure might be predicted very early, namely within the first 6 postoperative months. We conclude that surgical management of posterior cortex epilepsy may attain excellent results.

Drug-resistant parietal epilepsy: polymorphic ictal semiology does not preclude good post-surgical outcome.

We investigated the anatomo-electro-clinical features and clinical outcome of surgical resections strictly confined to the parietal lobe in 40 consecutive patients who received surgery for pharmacoresistant seizures. The population was subcategorized into a paediatric (11 subjects; mean age at surgery: 7.2+/-3.7 years) and an adult group (29 patients; mean age at surgery: 30+/-10.8 years). The paediatric group more frequently exhibited personal antecedents, neurological impairment, high seizure frequency, and dysplastic lesions. Nonetheless, compared with adults, children had better outcome and more frequently reached definitive drug discontinuation after surgery. After a mean follow-up of 9.4 years (range: 3.1-16.7), 30 subjects (75%) were classified as Engel Class I. The presence of multiple types of aura in the same patient, as well as a high incidence of secondary generalization, represented a characteristic feature of parietal seizures and did not correlate negatively with surgical outcome. A total resection of the epileptogenic zone and a localizing/regional interictal EEG were statistically significant predictive factors of outcome. Intracerebral investigation, performed in 55% of cases, contributed to complete tailored resections of the epileptogenic area and determination of prognosis. Frequent subjective manifestations of parietal lobe seizures, such as vertiginous, cephalic and visual-moving sensations, underscore their potential misdiagnosis as non-epileptic events.

Combining ESI, ASL and PET for quantitative assessment of drug-resistant focal epilepsy.

When localization of the epileptic focus is uncertain, the epileptic activity generator may be more accurately identified with non-invasive imaging techniques which could also serve to guide stereo-electroencephalography (sEEG) electrode implantation. The aim of this study was to assess the diagnostic value of perfusion magnetic resonance imaging with arterial spin labeling (ASL) in the identification of the epileptogenic zone, as compared to the more invasive positron-emission tomography (PET) and other established investigation methods for source imaging of electroencephalography (EEG) data. In 6 patients with drug-resistant focal epilepsy, standard video-EEG was performed to identify clinical seizure semeiology, and high-density EEG, ASL and FDG-PET to non-invasively localize the epileptic focus. A standardized source imaging procedure, low-resolution brain electromagnetic tomography constrained to the individual matter, was applied to the averaged spikes of high-density EEG. Quantification of current density, cerebral blood flow, and standardized uptake value were compared over the same anatomical areas. In most of the patients, source in the interictal phase was associated with an area of hypoperfusion and hypometabolism. Conversely, in the patients presenting with early post-ictal discharges, the brain area identified by electrical source imaging (ESI) as the generating zone appeared to be hyperperfused. In 2 patients in whom the focus remained uncertain, the postoperative follow-up showed the disappearance of epileptic activity. As an innovative and more comprehensive approach to the study of epilepsy, the combined use of ESI, perfusion MRI, and PET may play an increasingly important role in the non-invasive evaluation of patients with refractory focal epilepsy.

Human cortical activity evoked by gaze shift observation: an intracranial EEG study.

While is widely accepted that the posterior temporal region is activated during the observation of faces showing gaze shifts, it is still unclear whether its activity is stronger while observing direct or averted gaze. Furthermore, despite its assessed role in social cognition, studies describing an enhanced activity of the posterior temporal region during the observation of gaze aversion interpreted this activity in terms of spatial attention toward the target direction. This spatial attention interpretation is not easily reconcilable with the role of the posterior temporal region in social cognition, and an overarching view of its global cognitive function would be much more preferable. Here we used intracranial EEG to assess the precise spatial localization of the gaze shifts coding in the posterior temporal region, to assess its selectivity for direct versus averted gaze and to distinguish between a spatial-attentional and a social interpretations of gaze aversion. We found stronger activation during gaze aversion than direct gaze and lateral side switch observation, the latter indicating that the crucial aspect of gaze aversion is the prior presence of the eye contact and its interruption, and not the gaze direction. These results suggest a more social-oriented interpretation based on the view that among humans, gaze aversion signals a negative relational evaluation in social interaction.

Biomarkers of epileptogenic zone defined by quantified stereo-EEG analysis.

OBJECTIVE: In one third of patients with a diagnosis of pharmacoresistant focal epilepsy who are candidates for therapeutic surgery, cerebral areas responsible for seizure generation can be defined exclusively with invasive intracranial recordings. A correct presurgical identification of the epileptogenic zone (EZ) with intracranial electrodes has a direct impact on postsurgical outcome. We aimed at identifying biomarkers of the EZ based on computer-assisted inspection of intracranial electroencephalography (EEG). METHODS: Computer-driven intracranial EEG analysis in the domains of time, frequency, and space was retrospectively applied to a population of 10 patients with focal epilepsy to detect EZ electrophysiologic markers. Next, a prospective study was performed on 14 surgery candidate patients. The stereo-EEG computer-assisted analysis of EZ boundaries performed blind from patients data was compared to that defined with the traditional visual inspection completed by neurophysiologists. RESULTS: In the retrospective study, the EZ was characterized by the combined detection of three biomarkers observed at seizure onset: (1) fast activity at 80-120 Hz associated with (2) very slow transient polarizing shift and (3) voltage depression (flattening). Correlations between these indexes were calculated for each seizure. In the prospective study, the quantified analysis based on the three biomarkers confirmed a complete overlap between leads within the EZ identified by expert clinicians. In 2 of 14 patients the proposed biomarkers partially identified the EZ. SIGNIFICANCE: Our findings demonstrate and validate with a prospective unbiased study the use of three neurophysiologic intracranial EEG parameters as excellent biomarkers of ictogenesis and as reliable indicators of EZ boundaries.