Neurological morbidity of surgery for suprasylvian operculoinsular epilepsy.

OBJECTIVE: The objective of this study was to identify risk factors associated with surgery-related neurological morbidity in patients with drug-resistant epilepsy undergoing suprasylvian operculoinsular resections. As secondary outcomes, we also analyzed the risk factors for ischemic lesion (IL) of corona radiata and seizure recurrence. METHODS: A retrospective analysis was conducted on a cohort of patients who underwent suprasylvian operculoinsular resections for drug-resistant epilepsy. The association of several presurgical, surgical, and postsurgical factors with both primary (persistent neurological deficits) and secondary (structural abnormalities on postoperative magnetic resonance imaging [MRI] and seizure recurrence) postoperative outcomes was investigated with univariate and multivariate statistical analysis. RESULTS: The study included a total of 65 patients; 46.2% of patients exhibited postoperative neurological deficits, but only 12.3% experienced persistent deficits. On postoperative MRI, IL in the corona radiata and corticospinal tract Wallerian degeneration (CSTWd) were seen in 68% and 29% of cases, respectively. Only CSTWd was significantly associated with persistent neurological deficits (relative risk [RR] = 2.6). Combined operculoinsular resection (RR = 3.62) and surgery performed on the left hemisphere (RR = .37) were independently associated with IL in the corona radiata. Variables independently associated with CSTWd were the presence of malacic components in the IL (RR = 1.96), right central operculum resection (RR = 1.79), and increasing age at surgery (RR = 1.03). Sixty-two patients had a postoperative follow-up > 12 months (median = 56, interquartile range = 30.75-73.5), and 62.9% were in Engel class I at last outpatient control. The risk of seizure recurrence was reduced by selective opercular resection (RR = .25) and increased by the histological diagnosis of aspecific gliosis (RR = 1.39). SIGNIFICANCE: This study provides insights into the risk factors associated with surgery-related neurological morbidity, as well as further evidence on the postoperative occurrence of subcortical injury and seizure recurrence in epileptic patients undergoing suprasylvian operculoinsular resections. The findings highlighted in this study may be useful to better understand the processes supporting the increased surgical risk in the operculoinsular region.

Stereo-electroencephalography (SEEG)-Guided Surgery in Epilepsy With Cingulate Gyrus Involvement: Electrode Implantation Strategies and Postoperative Seizure Outcome.

SUMMARY: Surgical treatment of cingulate gyrus epilepsy is associated with good results on seizures despite its rarity and challenging aspects. Invasive EEG monitoring is often mandatory to assess the epileptogenic zone in these patients. To date, only small surgical series have been published, and a consensus about management of these complex cases did not emerge. The authors retrospectively analyzed a large surgical series of patients in whom at least part of the cingulate gyrus was confirmed as included in the epileptogenic zone by means of stereo-electroencephalography and was thus resected. One hundred twenty-seven patients were selected. Stereo-electroencephalography-guided implantation of intracerebral electrodes was performed in the right hemisphere in 62 patients (48.8%) and in the left hemisphere in 44 patients (34.7%), whereas 21 patients (16.5%) underwent bilateral implantations. The median number of implanted electrodes per patient was 13 (interquartile range 12-15). The median number of electrodes targeting the cingulate gyrus was 4 (interquartile range 3-5). The cingulate gyrus was explored bilaterally in 19 patients (15%). Complication rate was 0.8%. A favorable outcome (Engel class I) was obtained in 54.3% of patients, with a median follow-up of 60 months. The chance to obtain seizure freedom increased in cases in whom histologic diagnosis was type-IIb focal cortical dysplasia or tumor (mostly ganglioglioma or dysembryoplastic neuroepithelial tumor) and with male gender. Higher seizure frequency predicted better outcome with a trend toward significance. Our findings suggest that stereo-electroencephalography is a safe and effective methodology in achieving seizure freedom in complex cases of epilepsy with cingulate gyrus involvement.

Fast oscillations >40 Hz localize the epileptogenic zone: An electrical source imaging study using high-density electroencephalography.

OBJECTIVE: Fast Oscillations (FO) >40 Hz are a promising biomarker of the epileptogenic zone (EZ). Evidence using scalp electroencephalography (EEG) remains scarce. We assessed if electrical source imaging of FO using 256-channel high-density EEG (HD-EEG) is useful for EZ identification. METHODS: We analyzed HD-EEG recordings of 10 focal drug-resistant epilepsy patients with seizure-free postsurgical outcome. We marked FO candidate events at the time of epileptic spikes and verified them by screening for an isolated peak in the time-frequency plot. We performed electrical source imaging of spikes and FO within the Maximum Entropy of the Mean framework. Source localization maps were validated against the surgical cavity. RESULTS: We identified FO in five out of 10 patients who had a superficial or intermediate deep generator. The maximum of the FO maps was localized inside the cavity in all patients (100%). Analysis with a reduced electrode coverage using the 10-10 and 10-20 system showed a decreased localization accuracy of 60% and 40% respectively. CONCLUSIONS: FO recorded with HD-EEG localize the EZ. HD-EEG is better suited to detect and localize FO than conventional EEG approaches. SIGNIFICANCE: This study acts as proof-of-concept that FO localization using 256-channel HD-EEG is a viable marker of the EZ.

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.

Mirroring other's laughter. Cingulate, opercular and temporal contributions to laughter expression and observation.

Simulation theories predict that the observation of other's laughter modulates activity in the same centers controlling its production. Investigating this issue is particularly challenging, given the technical difficulties of studying laughter production. Previous observations from surgical patients reported laughter production following the electrical stimulation (ES) of the pregenual anterior cingulate (pACC), the frontal operculum (FO) and the temporal pole (TP), deemed to control emotional, communicative and cognitive aspects of laughter, respectively. Here we investigated which region is recruited during laughter observation and production, by adopting a twofold strategy which combines ES and intracranial recording in the same patients. We identified nine sites equally distributed in the pACC, FO and TP, where ES elicited laughter. Subsequently, we presented the patients with visual stimuli depicting dynamic (video) and static (pictures) expressions of laughter, along with emotional and neutral controls, while intracranially recording high-frequency gamma activity (50-150 Hz) from the same sites. pACC sites showed a selective activation during laughter observation, but only if laughter is presented in a dynamical fashion. FO and TP failed to respond during both dynamic and static expressions. We conclude that pACC host a mirror mechanism directly mapping other's laughter onto the neural substrate responsible for the production of emotional laughter.

Action execution and action observation elicit mirror responses with the same temporal profile in human SII.

The properties of the secondary somatosensory area (SII) have been described by many studies in monkeys and humans. Recent studies on monkeys, however, showed that beyond somatosensory stimuli, SII responds to a wider number of stimuli, a finding requiring a revision that human SII is purely sensorimotor. By recording cortical activity with stereotactic electroencephalography (stereo-EEG), we examined the properties of SI and SII in response to a motor task requiring reaching, grasping and manipulation, as well as the observation of the same actions. Furthermore, we functionally characterized this area with a set of clinical tests, including tactile, acoustical, and visual stimuli. The results showed that only SII activates both during execution and observation with a common temporal profile, whereas SI response were limited to execution. Together with their peculiar response to tactile stimuli, we conclude that the role of SII is pivotal also in the observation of actions involving haptic control.

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.

Hand posture as localizing sign in adult focal epileptic seizures.

OBJECTIVE: The aim of this study was to identify specific ictal hand postures (HPs) as localizing signs of the epileptogenic zone (EZ) in patients with frontal or temporal lobe epilepsy. METHODS: In this study, we retrospectively analyzed ictal semiology of 489 temporal lobe or frontal lobe seizures recorded over a 6-year period at the Seizure Disorder Center at University of California, Los Angeles in the USA (45 patients) or at the C. Munari Epilepsy Surgery Center at Niguarda Hospital in Milan, Italy (34 patients). Our criterion for EZ localization was at least 2 years of seizure freedom after surgery. We analyzed presence and latency of ictal HP. We then examined whether specific initial HPs are predictive for EZ localization. RESULTS: We found that ictal HPs were present in 72.5% of patients with frontal and 54.5% of patients with temporal lobe seizures. We divided HPs into 6 classes depending on the reciprocal position of the fingers ("fist," "cup," "politician's fist," "pincer," "extended hand," "pointing"). We found a striking correlation between EZ localization and ictal HP. In particular, fist and pointing HPs are strongly predictive of frontal lobe EZ; cup, politician's fist, and pincer are strongly predictive of temporal lobe EZ. INTERPRETATION: Our study offers simple ictal signs that appear to clarify differential diagnosis of temporal versus frontal lobe EZ localization. These results are meant to be used as a novel complementary tool during presurgical evaluation for epilepsy. At the same time, they give us important insight into the neurophysiology of hand movements. ANN NEUROL 2019;86:793-800.

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.

Tailored multilobar disconnective epilepsy surgery in the posterior quadrant.

OBJECTIVE: Surgical treatment of drug-resistant epilepsy originating from the posterior quadrant (PQ) of the brain often requires large multilobar resections, and disconnective techniques have been advocated to limit the risks associated with extensive tissue removal. Few previous studies have described a tailored temporoparietooccipital (TPO) disconnective approach; only small series with short postoperative follow-ups have been reported. The aim of the present study was to present a tailored approach to multilobar PQ disconnections (MPQDs) for epilepsy and to provide details about selection of patients, presurgical investigations, surgical technique, treatment safety profile, and seizure and cognitive outcome in a large, single-center series of patients with a long-term follow-up. METHODS: In this retrospective longitudinal study, the authors searched their prospectively collected database for patients who underwent MPQD for drug-resistant epilepsy in the period of 2005-2017. Tailored MPQDs were a posteriori grouped as follows: type I (classic full TPO disconnection), type II (partial TPO disconnection), type III (full temporooccipital [TO] disconnection), and type IV (partial TO disconnection), according to the disconnection plane in the occipitoparietal area. A bivariate statistical analysis was carried out to identify possible predictors of seizure outcome (Engel class I vs classes II-IV) among several presurgical, surgical, and postsurgical variables. Preoperative and postoperative cognitive profiles were also collected and evaluated. RESULTS: Forty-two consecutive patients (29 males, 24 children) met the inclusion criteria. According to the presurgical evaluation (including stereo-electroencephalography in 13 cases), 12 (28.6%), 24 (57.1%), 2 (4.8%), and 4 (9.5%) patients received a type I, II, III, or IV MPQD, respectively. After a mean follow-up of 80.6 months, 76.2% patients were in Engel class I at last contact; at 6 months and 2 and 5 years postoperatively, Engel class I was recorded in 80.9%, 74.5%, and 73.5% of cases, respectively. Factors significantly associated with seizure freedom were the occipital pattern of seizure semiology and the absence of bilateral interictal epileptiform abnormalities at the EEG (p = 0.02). Severe complications occurred in 4.8% of the patients. The available neuropsychological data revealed postsurgical improvement in verbal domains, whereas nonunivocal outcomes were recorded in the other functions. CONCLUSIONS: The presented data indicate that the use of careful anatomo-electro-clinical criteria in the presurgical evaluation allows for customizing the extent of surgical disconnections in PQ epilepsies, with excellent results on seizures and an acceptable safety profile.

Ipsilateral somatosensory responses in humans: the tonic activity of SII and posterior insular cortex.

In the present study, we mapped the spatio-temporal dynamics of cortical responses to ipsilateral median nerve stimulation using intracerebral recordings (stereo-EEG) in 38 drug-resistant epileptic patients. Furthermore, we compared the pattern of responsiveness obtained in the same leads across ipsilateral and contralateral stimulations. Ipsilateral responses were found mostly confined to SII and posterior insula, while no activity was found in ipsilateral SI. By examining the temporal profiles of activation, ipsilateral SII showed a prominent tonic pattern, while contralateral SII exhibited both phasic and tonic responses. Beyond the localization of the active cortical nodes, these data contributed to identify the cortico-cortical connections carrying the somatosensory information to the ipsilateral hemisphere, with a major role of transcallosal projections from contralateral SII. In light of previous literature and of its localization, the functional role possibly covered by long lasting discharge in SII and insular cortex is also discussed. Overall, the presence of tonic activities was neglected so far due to the impossibility to identify deep sources along with a resolved description of their time course. The use of stereo-EEG, instead, allows one to achieve a four-dimensional characterization, complementing the classical view about the somatosensory system organization.

Surgery in patients with childhood-onset epilepsy: analysis of complications and predictive risk factors for a severely complicated course.

OBJECT: To compare the occurrence of surgery-related complications in patients with childhood-onset focal epilepsy operated on in the paediatric or in the adult age. To investigate risk factors for surgery-related complications in the whole cohort, with special attention to age at surgery and severe morbidity. METHODS: A cohort of 1282 patients operated on for childhood-onset focal epilepsy was retrospectively analysed. Occurrence of surgery-related complications, including a severely complicated course (SCC: surgical complication requiring reoperation and/or permanent neurological deficit and/or death), was compared between patients operated on in the paediatric age (<16 year-old; 452 cases) and, respectively, in adulthood (≥16 year-old; 830 cases). The whole cohort of patients was also evaluated for risk factors for a SCC. RESULTS: At last contact (median follow-up 98 months), 74.5% of patients were in Engel's class I (78.0% of children and 73.0% of adults). One hundred patients (7.8%) presented a SCC (6.4% for children and 8.6% for adult patients). Postoperative intracranial haemorrhages occurred more frequently in adult cases. At multivariate analysis, increasing age at operation, multilobar surgery, resections in the rolandic/perirolandic and in insulo-opercular regions were independent risk factors for a SCC. CONCLUSIONS: Surgery for childhood-onset focal epilepsy provides excellent results on seizures and an acceptable safety profile at any age. Nevertheless, our results suggest that increasing age at surgery is associated with an increase in odds of developing severe surgery-related complications. These findings support the recommendation that children with drug-resistant, symptomatic (or presumed symptomatic) focal epilepsy should be referred for a surgical evaluation as early as possible after seizure onset.

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.

Corpus callosum atrophy and post-surgical seizures in temporal lobe epilepsy associated with hippocampal sclerosis.

OBJECTIVE: Our aim in this retrospective study was to explore whether corpus callosum atrophy could predict the post-surgical seizure control in patients with temporal lobe epilepsy associated with Hippocampal Sclerosis (HS). METHODS: We used the Corpus Callosum Index (CCI) obtained from best mid-sagittal T2/FLAIR or T1-weighted MRI at two time-points, more than one year apart. CCI has been mainly used in Multiple Sclerosis (MS), but not in epilepsy, so we tested the validity of our results performing a proof of concept cohort, incorporating MS patients with and without epilepsy. Then, we explored this measurement in a well-characterized and long-term cohort of patients with temporal lobe epilepsy associated with HS. RESULTS: In the proof of concept cohort (MS without epilepsy n:40, and MS with epilepsy, n:15), we found a larger CCI atrophy rate in MS patients with poor epilepsy control vs. MS without epilepsy (p:0.01). Then, in HS patients (n:74), annualized CCI atrophy rate was correlated with the long-term Engel scale (Rho:0.31, p:0.007). In patients with post-surgical seizure recurrence, a larger CCI atrophy rate was found one year before any seizure relapse. Univariate analysis showed an increased risk of seizure recurrence in males, higher pre-surgical seizure frequency, necessity of invasive EEG monitoring, and higher CCI atrophy rate. Two of these variables were independent predictors in the multivariate analysis, male gender (HR:4.87, p:0.002) and CCI atrophy rate (HR:1.21, p:0.001). CONCLUSION: We demonstrated that atrophy of the corpus callosum, using the CCI, is related with poor seizure control in two different neurological disorders presenting with epilepsy, which might suggest that corpus callosum atrophy obtained in early post-surgical follow-up, could be a biomarker for predicting recurrences and guiding treatment plans.

Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery.

BACKGROUND: Detailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy. METHODS: We report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug-resistant seizures in 36 centers from 12 European countries over 25 years. Histopathological diagnoses were determined through examination of the specimens in local hospitals (41%) or at the German Neuropathology Reference Center for Epilepsy Surgery (59%). RESULTS: The onset of seizures occurred before 18 years of age in 75.9% of patients overall, and 72.5% of the patients underwent surgery as adults. The mean duration of epilepsy before surgical resection was 20.1 years among adults and 5.3 years among children. The temporal lobe was involved in 71.9% of operations. There were 36 histopathological diagnoses in seven major disease categories. The most common categories were hippocampal sclerosis, found in 36.4% of the patients (88.7% of cases were in adults), tumors (mainly ganglioglioma) in 23.6%, and malformations of cortical development in 19.8% (focal cortical dysplasia was the most common type, 52.7% of cases of which were in children). No histopathological diagnosis could be established for 7.7% of the patients. CONCLUSIONS: In patients with drug-resistant focal epilepsy requiring surgery, hippocampal sclerosis was the most common histopathological diagnosis among adults, and focal cortical dysplasia was the most common diagnosis among children. Tumors were the second most common lesion in both groups. (Funded by the European Union and others.).

Increasing volume and complexity of pediatric epilepsy surgery with stable seizure outcome between 2008 and 2014: A nationwide multicenter study.

OBJECTIVE: The objective of the study was to assess common practice in pediatric epilepsy surgery in Italy between 2008 and 2014. METHODS: A survey was conducted among nine Italian epilepsy surgery centers to collect information on presurgical and postsurgical evaluation protocols, volumes and types of surgical interventions, and etiologies and seizure outcomes in pediatric epilepsy surgery between 2008 and 2014. RESULTS: Retrospective data on 527 surgical procedures were collected. The most frequent surgical approaches were temporal lobe resections and disconnections (133, 25.2%) and extratemporal lesionectomies (128, 24.3%); the most frequent etiologies were FCD II (107, 20.3%) and glioneuronal tumors (105, 19.9%). Volumes of surgeries increased over time independently from the age at surgery and the epilepsy surgery center. Engel class I was achieved in 73.6% of patients (range: 54.8 to 91.7%), with no significant changes between 2008 and 2014. Univariate analyses showed a decrease in the proportion of temporal resections and tumors and an increase in the proportion of FCDII, while multivariate analyses revealed an increase in the proportion of extratemporal surgeries over time. A higher proportion of temporal surgeries and tumors and a lower proportion of extratemporal and multilobar surgeries and of FCD were observed in low (<50surgeries/year) versus high-volume centers. There was a high variability across centers concerning pre- and postsurgical evaluation protocols, depending on local expertise and facilities. SIGNIFICANCE: This survey reveals an increase in volume and complexity of pediatric epilepsy surgery in Italy between 2008 and 2014, associated with a stable seizure outcome.

Epilepsy surgery of "low grade epilepsy associated neuroepithelial tumors": A retrospective nationwide Italian study.

OBJECTIVE: To analyze the attitude and results of Italian epilepsy surgery centers in the surgical management of "low grade epilepsy associated neuroepithelial tumors" (LEATs). METHODS: We conducted a retrospective study enrolling 339 consecutive patients with LEATs who underwent surgery between January 2009 and June 2015 at eight Italian epilepsy surgery centers. We compared demographic, clinical, pathologic, and surgical features of patients with favorable (Engel class I) and unfavorable (Engel class II, III, and IV) seizure outcome. In addition, we compared patients with tumor-associated focal cortical dysplasia (FCD) and patients with solitary tumors to identify factors correlated with FCD diagnosis. RESULTS: Fifty-five (98.2%) of 56 patients with medically controlled epilepsy were seizure-free after surgery, compared to 249 (88.0%) of 283 patients with refractory epilepsy. At multivariate analysis, three variables independently predict unfavorable seizure outcome in the drug-resistant group. Age at surgery is largely the most significant (p = 0.001), with an odds ratio (OR) of 1.04. This means that the probability of seizure recurrence grows by 4% for every waited year. The resection site is also significant (p = 0.039), with a relative risk (RR) of 1.99 for extratemporal tumors. Finally, the completeness of tumor resection has a trend toward significance (p = 0.092), with an RR of 1.82 for incomplete resection. Among pediatric patients, a longer duration of epilepsy was significantly associated with preoperative neuropsychological deficits (p < 0.001). A statistically significant association was observed between FCD diagnosis and the following variables: tailored surgery (p < 0.001), temporal resection (p = 0.001), and surgical center (p = 0.012). SIGNIFICANCE: Our nationwide LEATs study gives important insights on factors predicting seizure outcome in refractory epilepsy and determining variability in FCD detection. Timely surgery, regardless of pharmacoresistance and oriented to optimize epileptologic, neuropsychological, and oncologic outcomes should be warranted.

Seizure activity per se does not induce tissue damage markers in human neocortical focal epilepsy.

OBJECTIVE: The contribution of recurring seizures to the progression of epileptogenesis is debated. Seizure-induced brain damage is not conclusively demonstrated either in humans or in animal models of epilepsy. We evaluated the expression of brain injury biomarkers on postsurgical brain tissue obtained from 20 patients with frequent seizures and a long history of drug-resistant focal epilepsy. METHODS: The expression patterns of specific glial, neuronal, and inflammatory molecules were evaluated by immunohistochemistry in the core of type II focal cortical dysplasias (FCD-II), at the FCD boundary (perilesion), and in the adjacent normal-appearing area included in the epileptogenic region. We also analyzed surgical specimens from cryptogenic patients not presenting structural alterations at imaging. RESULTS: Astroglial and microglial activation, reduced neuronal density, perivascular CD3-positive T-lymphocyte clustering, and fibrinogen extravasation were demonstrated in the core of FCD-II lesions. No pathological immunoreactivity was observed outside the FCD-II or in cryptogenetic specimens, where the occurrence of interictal and ictal epileptiform activity was confirmed by either stereo-electroencephalography or intraoperative electrocorticography. INTERPRETATION: Recurrent seizures do not induce the expression of brain damage markers in nonlesional epileptogenic cortex studied in postsurgical tissue from cryptogenic and FCD patients. This evidence argues against the hypothesis that epileptiform activity per se contributes to focal brain injury, at least in the neocortical epilepsies considered here. Ann Neurol 2017;82:331-341.