Anatomo-functional basis of emotional and motor resonance elicited by facial expressions.

Simulation theories predict that the observation of other's expressions modulates neural activity in the same centers controlling their production. This hypothesis has been developed by two models, postulating that the visual input is directly projected either to the motor system for action recognition (motor resonance) or to emotional/interoceptive regions for emotional contagion and social synchronization (emotional resonance). Here we investigated the role of frontal/insular regions in the processing of observed emotional expressions by combining intracranial recording, electrical stimulation and effective connectivity. First, we intracranially recorded from prefrontal, premotor or anterior insular regions of 44 patients during the passive observation of emotional expressions, finding widespread modulations in prefrontal/insular regions (anterior cingulate cortex, anterior insula, orbitofrontal cortex and inferior frontal gyrus) and motor territories (rolandic operculum and inferior frontal junction). Subsequently, we electrically stimulated the activated sites, finding that (a) in the anterior cingulate cortex and anterior insula, the stimulation elicited emotional/interoceptive responses, as predicted by the 'emotional resonance model', (b) in the rolandic operculum it evoked face/mouth sensorimotor responses, in line with the 'motor resonance' model, and (c) all other regions were unresponsive or revealed functions unrelated to the processing of facial expressions. Finally, we traced the effective connectivity to sketch a network-level description of these regions, finding that the anterior cingulate cortex and the anterior insula are reciprocally interconnected while the rolandic operculum is part of the parieto-frontal circuits and poorly connected with the formers. These results support the hypothesis that the pathways hypothesized by the 'emotional resonance' and the 'motor resonance' models work in parallel, differing in terms of spatio-temporal fingerprints, reactivity to electrical stimulation and connectivity patterns.

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.

Magnetic susceptibility as a 1-year predictor of outcome in familial cerebral cavernous malformations: a pilot study.

OBJECTIVES: To test whether quantitative susceptibility mapping (QSM) of cerebral cavernous malformations (CCMs) assessed at baseline may predict the presence or absence of haemorrhagic signs at 1-year follow-up. METHODS: Familial CCM patients were enrolled in the longitudinal multicentre study Treat-CCM. The 3-T MRI scan allowed performing a semi-automatic segmentation of CCMs and computing the maximum susceptibility in each segmented CCM (QSMmax) at baseline. CCMs were classified as haemorrhagic and non-haemorrhagic at baseline and then subclassified according to the 1-year (t1) evolution. Between-group differences were tested, and the diagnostic accuracy of QSMmax in predicting the presence or absence of haemorrhagic signs in CCMs was calculated with ROC analyses. RESULTS: Thirty-three patients were included in the analysis, and a total of 1126 CCMs were segmented. QSMmax was higher in haemorrhagic CCMs than in non-haemorrhagic CCMs (p < 0.001). In haemorrhagic CCMs at baseline, the accuracy of QSMmax in differentiating CCMs that were still haemorrhagic from CCMs that recovered from haemorrhage at t1 calculated as area under the curve (AUC) was 0.78 with sensitivity 62.69%, specificity 82.35%, positive predictive value (PPV) 93.3% and negative predictive value (NPV) 35.9% (QSMmax cut-off ≥ 1462.95 ppb). In non-haemorrhagic CCMs at baseline, AUC was 0.91 in differentiating CCMs that bled at t1 from stable CCMs with sensitivity 100%, specificity 81.9%, PPV 5.1%, and NPV 100% (QSMmax cut-off ≥ 776.29 ppb). CONCLUSIONS: The QSMmax in CCMs at baseline showed high accuracy in predicting the presence or absence of haemorrhagic signs at 1-year follow-up. Further effort is required to test the role of QSM in follow-up assessment and therapeutic trials in multicentre CCM studies. KEY POINTS: • QSM in semi-automatically segmented CCM was feasible. • The maximum magnetic susceptibility in a single CCM at baseline may predict the presence or absence of haemorrhagic signs at 1-year follow-up. • Multicentric studies are needed to enforce the role of QSM in predicting the CCMs' haemorrhagic evolution in patients affected by familial and sporadic forms.

Tonic somatosensory responses and deficits of tactile awareness converge in the parietal operculum.

Although clinical neuroscience and the neuroscience of consciousness have long sought mechanistic explanations of tactile-awareness disorders, mechanistic insights are rare, mainly because of the difficulty of depicting the fine-grained neural dynamics underlying somatosensory processes. Here, we combined the stereo-EEG responses to somatosensory stimulation with the lesion mapping of patients with a tactile-awareness disorder, namely tactile extinction. Whereas stereo-EEG responses present different temporal patterns, including early/phasic and long-lasting/tonic activities, tactile-extinction lesion mapping co-localizes only with the latter. Overlaps are limited to the posterior part of the perisylvian regions, suggesting that tonic activities may play a role in sustaining tactile awareness. To assess this hypothesis further, we correlated the prevalence of tonic responses with the tactile-extinction lesion mapping, showing that they follow the same topographical gradient. Finally, in parallel with the notion that visuotactile stimulation improves detection in tactile-extinction patients, we demonstrated an enhancement of tonic responses to visuotactile stimuli, with a strong voxel-wise correlation with the lesion mapping. The combination of these results establishes tonic responses in the parietal operculum as the ideal neural correlate of tactile awareness.

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.

Temporal lobe epilepsy surgery in children and adults: A multicenter study.

OBJECTIVE: To assess seizure and cognitive outcomes and their predictors in children (<16 years at surgery) and adults undergoing temporal lobe epilepsy (TLE) surgery in eight Italian centers. METHODS: This is a retrospective multicenter study. We performed a descriptive analysis and subsequently carried out multivariable mixed-effect models corrected for multiple comparisons. RESULTS: We analyzed data from 511 patients (114 children) and observed significant differences in several clinical features between adults and children. The possibility of achieving Engel class IA outcome and discontinuing antiepileptic drugs (AEDs) at last follow-up (FU) was significantly higher in children (P = .006 and < .0001). However, percentages of children and adults in Engel class I at last FU (mean ± SD, 45.9 ± 17 months in children; 45.9 ± 20.6 months in adults) did not differ significantly. We identified different predictors of seizure outcome in children vs adults and at short- vs long-term FU. The only variables consistently associated with class I outcome over time were postoperative electroencephalography (EEG) in adults (abnormal, improved,odds ratio [OR] = 0.414, P = .023, Q = 0.046 vs normal, at 2-year FU and abnormal, improved, OR = 0.301, P = .001, Q = 0.002 vs normal, at last FU) and the completeness of resection of temporal magnetic resonance (MR) abnormalities other than hippocampal sclerosis in children (OR = 7.93, P = .001, Q = 0.003, at 2-year FU and OR = 45.03, P < .0001, Q < 0.0001, at last FU). Cognitive outcome was best predicted by preoperative performances in either age group. SIGNIFICANCE: Clinical differences between adult and pediatric patients undergoing TLE surgery are reflected in differences in long-term outcomes and predictors of failures. Children are more likely to achieve sustained seizure freedom and withdraw AEDs after TLE surgery. Earlier referral should be encouraged as it can improve surgical outcome.

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.

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.

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.

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.

Localizing hidden Interictal Epileptiform Discharges with simultaneous intracerebral and scalp high-density EEG recordings.

BACKGROUND: Scalp EEG is one of the main tools in the clinical evaluation of epilepsy. In some cases intracranial Interictal Epileptiform Discharges (IEDs) are not visible from the scalp. Recent studies have shown the feasibility of revealing them in the EEG if their timings are extracted from simultaneous intracranial recordings, but their potential for the localization of the epileptogenic zone is not yet well defined. NEW METHOD: We recorded simultaneous high-density EEG (HD-EEG) and stereo-electroencephalography (SEEG) during interictal periods in 8 patients affected by drug-resistant focal epilepsy. We identified IEDs in the SEEG and systematically analyzed the time-locked signals on the EEG by means of evoked potentials, topographical analysis and Electrical Source Imaging (ESI). The dataset has been standardized and is being publicly shared. RESULTS: Our results showed that IEDs that were not clearly visible at single-trials could be uncovered by averaging, in line with previous reports. They also showed that their topographical voltage distributions matched the position of the SEEG electrode where IEDs had been identified, and that ESI techniques can reconstruct it with an accuracy of ∼2 cm. Finally, the present dataset provides a reference to test the accuracy of different methods and parameters. COMPARISON WITH EXISTING METHODS: Our study is the first to systematically compare ESI methods on simultaneously recorded IEDs, and to share a public resource with in-vivo data for their evaluation. CONCLUSIONS: Simultaneous HD-EEG and SEEG recordings can unveil hidden IEDs whose origins can be reconstructed using topographical and ESI analyses, but results depend on the selected methods and parameters.

Thalamic feedback shapes brain responses evoked by cortical stimulation in mice and humans.

Cortical stimulation with single pulses is a common technique in clinical practice and research. However, we still do not understand the extent to which it engages subcortical circuits which contribute to the associated evoked potentials (EPs). Here we find that cortical stimulation generates remarkably similar EPs in humans and mice, with a late component similarly modulated by the subject's behavioral state. We optogenetically dissect the underlying circuit in mice, demonstrating that the late component of these EPs is caused by a thalamic hyperpolarization and rebound. The magnitude of this late component correlates with the bursting frequency and synchronicity of thalamic neurons, modulated by the subject's behavioral state. A simulation of the thalamo-cortical circuit highlights that both intrinsic thalamic currents as well as cortical and thalamic GABAergic neurons contribute to this response profile. We conclude that the cortical stimulation engages cortico-thalamo-cortical circuits highly preserved across different species and stimulation modalities.

A case of clinical worsening after stereo-electroencephalographic-guided radiofrequency thermocoagulation in a patient with polymicrogyria.

Radiofrequency thermocoagulation (RF-TC) is a wide-used procedure for drug-resistant epilepsy. The technique is considered safe with an overall risk of 1.1% of permanent complications, mainly focal neurological deficits. We report the case of a patient with drug-resistant epilepsy who complained of immediate seizure worsening and an unexpected event seven months following RF-TC. A 35-year-old male with drug-resistant epilepsy from the age of 18 years underwent stereoelectroencephalography (SEEG) implantation for a right peri-silvian polymicrogyria. He was excluded from surgery due to extent of the epileptogenic zone and the risk of visual field deficits. RF-TC was attempted to ablate the most epileptogenic zone identified by SEEG. After RF-TC, the patient reported an increase in seizure severity/frequency and experienced episodes of postictal psychosis. Off-label cannabidiol treatment led to improved seizure control and resolution of postictal psychosis. Patients with polymicrogyria (PwP) may present with a disruption of normal anatomy and the co-existence between epileptogenic zone and eloquent cortex within the malformation. RF-TC should be considered in PwP when they are excluded from surgery for prognostic and palliative purposes. However, given the complex interplay between pathological and electrophysiological networks in these patients, the remote possibility of clinical exacerbation after RF-TC should also be taken into account.

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.

Event-related causality in stereo-EEG discriminates syntactic processing of noun phrases and verb phrases.

Objective.Syntax involves complex neurobiological mechanisms, which are difficult to disentangle for multiple reasons. Using a protocol able to separate syntactic information from sound information we investigated the neural causal connections evoked by the processing of homophonous phrases, i.e. with the same acoustic information but with different syntactic content. These could be either verb phrases (VP) or noun phrases.Approach. We used event-related causality from stereo-electroencephalographic recordings in ten epileptic patients in multiple cortical and subcortical areas, including language areas and their homologous in the non-dominant hemisphere. The recordings were made while the subjects were listening to the homophonous phrases.Main results.We identified the different networks involved in the processing of these syntactic operations (faster in the dominant hemisphere) showing that VPs engage a wider cortical and subcortical network. We also present a proof-of-concept for the decoding of the syntactic category of a perceived phrase based on causality measures.Significance. Our findings help unravel the neural correlates of syntactic elaboration and show how a decoding based on multiple cortical and subcortical areas could contribute to the development of speech prostheses for speech impairment mitigation.

Language lateralization mapping (reversibly) masked by non-dominant focal epilepsy: a case report.

Language lateralization in patients with focal epilepsy frequently diverges from the left-lateralized pattern that prevails in healthy right-handed people, but the mechanistic explanations are still a matter of debate. Here, we debate the complex interaction between focal epilepsy, language lateralization, and functional neuroimaging techniques by introducing the case of a right-handed patient with unaware focal seizures preceded by aphasia, in whom video-EEG and PET examination suggested the presence of focal cortical dysplasia in the right superior temporal gyrus, despite a normal structural MRI. The functional MRI for language was inconclusive, and the neuropsychological evaluation showed mild deficits in language functions. A bilateral stereo-EEG was proposed confirming the right superior temporal gyrus origin of seizures, revealing how ictal aphasia emerged only once seizures propagated to the left superior temporal gyrus and confirming, by cortical mapping, the left lateralization of the posterior language region. Stereo-EEG-guided radiofrequency thermocoagulations of the (right) focal cortical dysplasia not only reduced seizure frequency but led to the normalization of the neuropsychological assessment and the "restoring" of a classical left-lateralized functional MRI pattern of language. This representative case demonstrates that epileptiform activity in the superior temporal gyrus can interfere with the functioning of the contralateral homologous cortex and its associated network. In the case of presurgical evaluation in patients with epilepsy, this interference effect must be carefully taken into consideration. The multimodal language lateralization assessment reported for this patient further suggests the sensitivity of different explorations to this interference effect. Finally, the neuropsychological and functional MRI changes after thermocoagulations provide unique cues on the network pathophysiology of focal cortical dysplasia and the role of diverse techniques in indexing language lateralization in complex scenarios.

Surgery for tuberous sclerosis complex-related epilepsy: Risk factors for an unfavorable seizure outcome.

PURPOSE: This study aimed to identify risk factors of postoperative seizure outcome in a consecutive cohort of patients operated on for TSC-related focal epilepsy, by evaluating several presurgical and surgical variables, including also MRI-visible brain abnormalities other than cortical tubers. METHODS: This retrospective study included 51 patients surgically treated for drug-resistant focal epilepsy with a histological diagnosis of cortical tuber and followed for at least 12 months postoperatively. We investigated the association between several potentially explanatory variables and seizure outcome by univariate and multivariate analysis in the whole cohort and in the subgroups of patients with single and multiple tubers, respectively. RESULTS: The median postoperative follow-up was 115 months (IQR 63-168) and 54.9% of patients were in Engel's class I at final control. In the whole cohort, variables independently associated with an unfavorable seizure outcome (Engel's classes II-IV) were: preoperative non-focal interictal EEG (RR 5, CI 2.46-6.39), presence of sub-ependymal nodules (SEN) (RR 3.53, CI 1.71-4.56) and seizure onset before the first year of age (RR 3.56, CI 0.91-6.89). Non-focal interictal EEG was independently associated with an unfavorable outcome also in the subgroup of patients with multiple tubers (RR 4.34, CI 2.23-5.37), while the presence of SEN (p=0.0221) and of extra-central nervous system lesions (p= 0.0152) predicted an unfavorable seizure outcome in patients with a single tuber. CONCLUSION: Surgery represents an effective option for seizure control in patients with TSC-related epilepsy. The identification of preoperative risk factors for seizure outcome could be helpful for optimizing patients' selection for surgery and pre-surgical counseling.

A semi-automatic registration protocol to match ex-vivo high-field 7T MR images and histological slices in surgical samples from patients with drug-resistant epilepsy.

BACKGROUND: MRI is a fundamental tool to detect brain structural anomalies and improvement in this technique has the potential to visualize subtle abnormalities currently undetected. Correlation between pre-operative MRI and histopathology is required to validate the neurobiological basis of MRI abnormalities. However, precise MRI-histology matching is very challenging with the surgical samples. We previously developed a coregistration protocol to match the in-vivo MRI with ex-vivo MRI obtained from surgical specimens. Now, we complete the process to successfully align ex-vivo MRI data with the proper digitalized histological sections in an automatic way. NEW METHOD: The implemented pipeline is composed by the following steps: a) image pre-processing made of MRI and histology volumes conversion and masking; b) gross rigid body alignment between MRI volume and histology virtual slides; c) rigid alignment between each MRI section and histology slice and estimate of the correlation coefficient for each step to select the MRI slice that best matches histology; d) final linear registration of the selected slices. RESULTS: This method is fully automatic, except for the first masking step, fast and reliable in comparison to the manual one, as assessed using a Bland-Altman plot. COMPARISON WITH EXISTING METHODS: The visual assessment usually employed for choosing the best fitting ex-vivo MRI slice for each stained section takes hours and requires practice. Goubran et al. (2015) proposed an iterative registration protocol but its aim and methods were different from ours. No others similar methods are reported in the literature. CONCLUSIONS: This protocol completes our previous pipeline. The ultimate goal will be to apply the entire process to finely investigate the relationship between clinical MRI data and histopathological features in patients with drug-resistant epilepsy.