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.

An in-vivo validation of ESI methods with focal sources.

Electrophysiological source imaging (ESI) aims at reconstructing the precise origin of brain activity from measurements of the electric field on the scalp. Across laboratories/research centers/hospitals, ESI is performed with different methods, partly due to the ill-posedness of the underlying mathematical problem. However, it is difficult to find systematic comparisons involving a wide variety of methods. Further, existing comparisons rarely take into account the variability of the results with respect to the input parameters. Finally, comparisons are typically performed using either synthetic data, or in-vivo data where the ground-truth is only roughly known. We use an in-vivo high-density EEG dataset recorded during intracranial single pulse electrical stimulation, in which the true sources are substantially dipolar and their locations are precisely known. We compare ten different ESI methods, using their implementation in the MNE-Python package: MNE, dSPM, LORETA, sLORETA, eLORETA, LCMV beamformers, irMxNE, Gamma Map, SESAME and dipole fitting. We perform comparisons under multiple choices of input parameters, to assess the accuracy of the best reconstruction, as well as the impact of such parameters on the localization performance. Best reconstructions often fall within 1 cm from the true source, with most accurate methods hitting an average localization error of 1.2 cm and outperforming least accurate ones erring by 2.5 cm. As expected, dipolar and sparsity-promoting methods tend to outperform distributed methods. For several distributed methods, the best regularization parameter turned out to be the one in principle associated with low SNR, despite the high SNR of the available dataset. Depth weighting played no role for two out of the six methods implementing it. Sensitivity to input parameters varied widely between methods. While one would expect high variability being associated with low localization error at the best solution, this is not always the case, with some methods producing highly variable results and high localization error, and other methods producing stable results with low localization error. In particular, recent dipolar and sparsity-promoting methods provide significantly better results than older distributed methods. As we repeated the tests with "conventional" (32 channels) and dense (64, 128, 256 channels) EEG recordings, we observed little impact of the number of channels on localization accuracy; however, for distributed methods denser montages provide smaller spatial dispersion. Overall findings confirm that EEG is a reliable technique for localization of point sources and therefore reinforce the importance that ESI may have in the clinical context, especially when applied to identify the surgical target in potential candidates for epilepsy surgery.

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.

A comparative study between state-of-the-art MRI deidentification and AnonyMI, a new method combining re-identification risk reduction and geometrical preservation.

Deidentifying MRIs constitutes an imperative challenge, as it aims at precluding the possibility of re-identification of a research subject or patient, but at the same time it should preserve as much geometrical information as possible, in order to maximize data reusability and to facilitate interoperability. Although several deidentification methods exist, no comprehensive and comparative evaluation of deidentification performance has been carried out across them. Moreover, the possible ways these methods can compromise subsequent analysis has not been exhaustively tested. To tackle these issues, we developed AnonyMI, a novel MRI deidentification method, implemented as a user-friendly 3D Slicer plugin-in, which aims at providing a balance between identity protection and geometrical preservation. To test these features, we performed two series of analyses on which we compared AnonyMI to other two state-of-the-art methods, to evaluate, at the same time, how efficient they are at deidentifying MRIs and how much they affect subsequent analyses, with particular emphasis on source localization procedures. Our results show that all three methods significantly reduce the re-identification risk but AnonyMI provides the best geometrical conservation. Notably, it also offers several technical advantages such as a user-friendly interface, multiple input-output capabilities, the possibility of being tailored to specific needs, batch processing and efficient visualization for quality assurance.

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.

Knowledge-based automated planning system for StereoElectroEncephaloGraphy: A center-based scenario.

Surgical planning for StereoElectroEncephaloGraphy (SEEG) is a complex and patient specific task, where the experience and medical workflow of each institution may influence the final planning choices. To account for this variability, we developed a data-based Computer Assisted Planning (CAP) solution able to exploit the knowledge extracted by past cases. By the analysis of retrospective patients' data sets, our system proposes a pool of trajectories commonly used by the institution, which can be selected to initialize a new patient plan. An optimization framework adapts those to the patient's anatomy by optimizing clinical requirements (e.g. distance from vessel, gray matter recording and insertion angle), and adapting its strategy based on the trajectory type selected.The system has been customized based on the data of a single institution. Two neurosurgeons, working in a high-volume hospital, have validated it by using 15 retrospective patient data sets, with more than 200 trajectories reviewed. Both surgeons considered ~81% of the optimized trajectories as clinically feasible (75% inter-rater reliability). Quantitative comparison of distance from vessels, insertion angle and gray matter recording index showed that the optimized trajectories reached superior or comparable values with respect to the original manual plans. The results suggest that a tailored center-based solution could increase the acceptance rate of the automated trajectories proposed.

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.

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.

SEEG assistant: a 3DSlicer extension to support epilepsy surgery.

BACKGROUND: In the evaluation of Stereo-Electroencephalography (SEEG) signals, the physicist's workflow involves several operations, including determining the position of individual electrode contacts in terms of both relationship to grey or white matter and location in specific brain regions. These operations are (i) generally carried out manually by experts with limited computer support, (ii) hugely time consuming, and (iii) often inaccurate, incomplete, and prone to errors. RESULTS: In this paper we present SEEG Assistant, a set of tools integrated in a single 3DSlicer extension, which aims to assist neurosurgeons in the analysis of post-implant structural data and hence aid the neurophysiologist in the interpretation of SEEG data. SEEG Assistant consists of (i) a module to localize the electrode contact positions using imaging data from a thresholded post-implant CT, (ii) a module to determine the most probable cerebral location of the recorded activity, and (iii) a module to compute the Grey Matter Proximity Index, i.e. the distance of each contact from the cerebral cortex, in order to discriminate between white and grey matter location of contacts. Finally, exploiting 3DSlicer capabilities, SEEG Assistant offers a Graphical User Interface that simplifies the interaction between the user and the tools. SEEG Assistant has been tested on 40 patients segmenting 555 electrodes, and it has been used to identify the neuroanatomical loci and to compute the distance to the nearest cerebral cortex for 9626 contacts. We also performed manual segmentation and compared the results between the proposed tool and gold-standard clinical practice. As a result, the use of SEEG Assistant decreases the post implant processing time by more than 2 orders of magnitude, improves the quality of results and decreases, if not eliminates, errors in post implant processing. CONCLUSIONS: The SEEG Assistant Framework for the first time supports physicists by providing a set of open-source tools for post-implant processing of SEEG data. Furthermore, SEEG Assistant has been integrated into 3D Slicer, a software platform for the analysis and visualization of medical images, overcoming limitations of command-line tools.

Type II focal cortical dysplasia: Ex vivo 7T magnetic resonance imaging abnormalities and histopathological comparisons.

OBJECTIVE: In the present report, the correlations between ex vivo high-resolution imaging and specific histological and ultrastructural patterns in type II focal cortical dysplasia (FCD) have been studied to explain the differences in the magnetic resonance imaging (MRI) detection of dysplasia and to contribute to the presurgical imaging evaluation of this pathology. METHODS: Surgical specimens from 13 patients with FCD IIa/b were submitted to 7T MRI scanning, and then analyzed histologically and ultrastructurally to compare the results with the MRI findings. Region of interest (ROI)-based measures on T2-weighted images (T2wi) were quantitatively evaluated in the lesion and in adjacent perilesional gray and white matter. RESULTS: Matched histological sections and 7T T2wi showed that the core of the lesion was characterized by patchy aggregates of abnormal cells and fiber disorganization related to inhomogeneity of intracortical signal intensity. The quantitative approach on T2wi can help to distinguish the lesions and perilesional areas even in a clinical MRI-negative case. The ultrastructural study showed that the strong signal hyperintensity in the white matter of FCD IIb was related to a dysmyelination process associated with severe fiber loss and abnormal cells. Less severe histopathological features were found in FCD IIa, thus reflecting their less evident MRI alterations. INTERPRETATION: We suggest that white matter abnormalities in type IIb FCD are due to defects of the myelination processes and maturation, impaired by the presence of balloon cells. To reveal the presence and the border of type II cortical dysplasia on MRI, a quantitative ROI-based analysis (coefficient of variation) is also proposed.

Stereo-EEG-guided radiofrequency thermocoagulations.

The rationale and the surgical technique of stereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) in the epileptogenic zone (EZ) of patients with difficult-to-treat focal epilepsy are described in this article. The application of the technique in pediatric patients is also detailed. Stereotactic ablative procedures by RF-TC have been employed in the treatment of epilepsy since the middle of the last century. This treatment option has gained new popularity in recent decades, mainly because of the availability of modern imaging techniques, which allow accurate targeting of intracerebral epileptogenic structures. SEEG is a powerful tool for identifying the EZ in the most challenging cases of focal epilepsy by recording electrical activity with tailored stereotactic implantation of multilead intracerebral electrodes. The same recording electrodes may be used to place thermocoagulative lesions in the EZ, following the indications provided by intracerebral monitoring. The technical details of SEEG implantation and of SEEG-guided RF-TC are described herein, with special attention to the employment of the procedure in pediatric cases. SEEG-guided RF-TC offers a potential therapeutic option based on robust electroclinical evidence with acceptable risks and costs. The procedure may be performed in patients who, according to SEEG recording, are not eligible for resective surgery, and it may be an alternative to resective surgery in a small subset of operable 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.

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.

Surgical outcomes in two different age groups with Focal Cortical Dysplasia type II: Any real difference?

OBJECTIVE: Focal Cortical Dysplasias (FCDs) represent a common architectural cortical disorder underlying drug-resistant focal epilepsy. So far, studies aimed at evaluating whether age at surgery is a factor influencing surgical outcome are lacking, so that data on the comparison between patients harboring Type II FCD operated at younger age and those operated at adult age are still scarce. We compared presurgical clinical features and surgical outcomes of patients with histopathologically diagnosed Type II FCD undergoing surgery at an earlier age with those operated after 20 years of age. METHODS: We retrospectively analyzed 1660 consecutive patients operated at the "Claudio Munari" Epilepsy Surgery Centre. There were 289 patients (17.4%) with a neuropathological diagnosis of Type II FCD. We included two different groups of patients, the first one including patients operated on at less than 6years, the second sharing the same seizure onset age but with delayed surgery, carried out after the age of 20. Seizure characteristics and, neuropsychological and postoperative seizure outcomes were evaluated by study group. RESULTS: Forty patients underwent surgery before the age of 6 and 66 patients after the age of 20. Surgical outcome was favorable in the whole population (72.6% were classified in Engel's Class Ia+Ic), independently from age at surgery. In the children group, 32 patients were classified in Class I, including 30 (75%) children in classes Ia and Ic. In the adult group, 53 belonged to Class I of whom 47 (71%) were in classes Ia and Ic. The percentage of permanent complications, the surgical outcomes, and AED withdrawal did not significantly differ by study group. CONCLUSION: Our results indicate that there is no difference between the groups, suggesting that outcome depends mainly on the histological findings and not on timing of surgery.

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.

A new tool for touch-free patient registration for robot-assisted intracranial surgery: application accuracy from a phantom study and a retrospective surgical series.

OBJECTIVE The purpose of this study was to compare the accuracy of Neurolocate frameless registration system and frame-based registration for robotic stereoelectroencephalography (SEEG). METHODS The authors performed a 40-trajectory phantom laboratory study and a 127-trajectory retrospective analysis of a surgical series. The laboratory study was aimed at testing the noninferiority of the Neurolocate system. The analysis of the surgical series compared Neurolocate-based SEEG implantations with a frame-based historical control group. RESULTS The mean localization errors (LE) ± standard deviations (SD) for Neurolocate-based and frame-based trajectories were 0.67 ± 0.29 mm and 0.76 ± 0.34 mm, respectively, in the phantom study (p = 0.35). The median entry point LE was 0.59 mm (interquartile range [IQR] 0.25-0.88 mm) for Neurolocate-registration-based trajectories and 0.78 mm (IQR 0.49-1.08 mm) for frame-registration-based trajectories (p = 0.00002) in the clinical study. The median target point LE was 1.49 mm (IQR 1.06-2.4 mm) for Neurolocate-registration-based trajectories and 1.77 mm (IQR 1.25-2.5 mm) for frame-registration-based trajectories in the clinical study. All the surgical procedures were successful and uneventful. CONCLUSIONS The results of the phantom study demonstrate the noninferiority of Neurolocate frameless registration. The results of the retrospective surgical series analysis suggest that Neurolocate-based procedures can be more accurate than the frame-based ones. The safety profile of Neurolocate-based registration should be similar to that of frame-based registration. The Neurolocate system is comfortable, noninvasive, easy to use, and potentially faster than other registration devices.

Different parvalbumin and GABA expression in human epileptogenic focal cortical dysplasia.

OBJECTIVE: Several studies have reported that inhibitory networks are altered in dysplastic tissue obtained from epilepsy surgery specimens. A consistent decrease in the number of inhibitory interneuronal subpopulation that expresses parvalbumin (PV) was reported in postsurgical tissue from patients with focal cortical dysplasia (FCD). We tested if the decrease in PV protein expression observed in epileptic tissue corresponds to a parallel impairment in the γ-aminobutyric acid (GABA)ergic compartment. METHODS: We analyzed postsurgical tissue from 30 surgically treated patients who underwent surgery for intractable epilepsy including 26 patients with FCD (types I, II, and III) and 4 patients without any microscopic visible lesion (cryptogenic) as controls. Serial sections were processed using in situ hybridization with GAD-65 and GAD-67 probes and immunocytochemistry with antibody against PV. The density of inhibitory PV-immunoreactive interneurons in relation to GABAergic cells was estimated in controls and in all different pathologic groups by using a two- and three-dimensional (2D and 3D) cell-counting technique. Field fraction and line profile analyses were added to estimate immunostaining proportion and distribution of PV signal generated in gray matter. RESULTS: A reduction of PV-positive cells and PV-immunoreactivity was observed exclusively in FCD type I/III specimens compared with cryptogenic tissue from control patients with a poor postsurgical outcome. In FCD type II, a profound rearrangement in the cortical distribution of PV immunoreactivity was observed, without a quantitative reduction of the number of neurons and terminals. In situ hybridization did not reveal significant variations of GAD expression in any FCD subtype. SIGNIFICANCE: Our study suggests a preservation of inhibitory networks in FCD postsurgical tissue, demonstrated by a substantial normal count of GABAergic neurons. A selective PV expression impairment is demonstrated in FCD type I and III and an abnormal, but not reduced, distribution of PV cells and terminals is confirmed in type II FCD. Possible functional consequences are discussed.