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

Hippocampal sclerosis (HS) may be associated with focal cortical dysplasia IIIa (FCD IIIa) in patients undergoing surgery for temporal lobe epilepsy (TLE).

ObjectiveDirect 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 methodWe 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.ResultsOf 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.ConclusionAmong the already known predictors outcome, seizure induction by LFS therefore represents a positive predictive factor for seizure outcome after surgery.

Graphical Abstract

Purpose: Accurate segmentation of brain resection cavities (RCs) aids in postoperative analysis and determining follow-up treatment. Convolutional neural networks (CNNs) are the state-of-the-art image segmentation technique, but require large annotated datasets for training. Annotation of 3D medical images is time-consuming, requires highly trained raters and may suffer from high inter-rater variability. Self-supervised learning strategies can leverage unlabeled data for training. Methods: We developed an algorithm to simulate resections from preoperative magnetic resonance images (MRIs). We performed self-supervised training of a 3D CNN for RC segmentation using our simulation method. We curated EPISURG, a dataset comprising 430 postoperative and 268 preoperative MRIs from 430 refractory epilepsy patients who underwent resective neurosurgery. We fine-tuned our model on three small annotated datasets from different institutions and on the annotated images in EPISURG, comprising 20, 33, 19 and 133 subjects. Results: The model trained on data with simulated resections obtained median (interquartile range) Dice score coefficients (DSCs) of 81.7 (16.4), 82.4 (36.4), 74.9 (24.2) and 80.5 (18.7) for each of the four datasets. After fine-tuning, DSCs were 89.2 (13.3), 84.1 (19.8), 80.2 (20.1) and 85.2 (10.8). For comparison, inter-rater agreement between human annotators from our previous study was 84.0 (9.9). Conclusion: We present a self-supervised learning strategy for 3D CNNs using simulated RCs to accurately segment real RCs on postoperative MRI. Our method generalizes well to data from different institutions, pathologies and modalities. Source code, segmentation models and the EPISURG dataset are available at https://github.com/fepegar/resseg-ijcars.

Here we describe a rare case of Capgras delusion – a misidentification syndrome characterized by the belief that a person has been replaced by an imposter– in a patient without evident neurological or psychiatric symptoms. Intriguingly, delusional belief was selective for both person and modality, as the patient believed that his son – not his daughter or other relatives – was substituted with an imposter only while being in presence of him and looking at his face, but not when merely listening to his voice.

Unequivocally demonstrating the presence of multisensory signals at the earliest stages of cortical processing remains challenging in humans. In our study, we relied on the unique spatio-temporal resolution provided by intracranial stereotactic electroencephalographic (SEEG) recordings in patients with drug-resistant epilepsy to characterize the signal extracted from early visual (calcarine and pericalcarine) and auditory (Heschl's gyrus and planum temporale) regions during a simple audio-visual oddball task. We provide evidences that both cross-modal responses (visual responses in auditory cortex or the reverse) and multisensory processing (alteration of the unimodal responses during bimodal stimulation) can be observed in intracranial event-related potentials (iERPs) and in power modulations of oscillatory activity at different temporal scales within the first 150 msec after stimulus onset. The temporal profiles of the iERPs are compatible with the hypothesis that MSI occurs by means of direct pathways linking early visual and auditory regions. Our data indicate, moreover, that MSI mainly relies on modulations of the low-frequency bands (foremost the theta band in the auditory cortex and the alpha band in the visual cortex), suggesting the involvement of feedback pathways between the two sensory regions. Remarkably, we also observed high-gamma power modulations by sounds in the early visual cortex, thus suggesting the presence of neuronal populations involved in auditory processing in the calcarine and pericalcarine region in humans.

Standardized Workflow for Advanced Neuroimaging in Epilepsy(SWANe) software provides researchers with a platform to analyze multimodal imaging modalities and to automatically combine the data from each modality into an integrating three-dimensional fashion. The software comes with a GUI and is designed to be user-friendly and for the not-technical public. SWANe is implemented in Python language and falls within the MIT license. The toolbox builds on a combination of existing methods to improve the user's power to perform analyses on different types of structural, functional, and metabolic imaging. SWANe has been developed in principle for the study of focal epilepsies of any age but it might be prospectively applied in different neurological diseases and for presurgical planning.

Musicogenic epilepsy is rare focal epilepsy in which seizures are triggered by music. Both spontaneous and reflexes seizures may occur. To date there are limited data about this epilepsy, particularly about its etiopathogenesis. We report the clinical, neurophysiological and imaging data about musicogenic epilepsy in a patient who underwent Stereo-electroencephalography (SEEG) study.

ObjectTo 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.MethodsA 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.ResultsAt 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.ConclusionsSurgery 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.

Focal epilepsy is a neurological disease that can be surgically treated by removing area of the brain generating the seizures. The stereotactic electroencephalography (SEEG) procedure allows patient brain activity to be recorded in order to localize the onset of seizures through the placement of intracranial electrodes. The planning phase can be cumbersome and very time consuming, and no quantitative information is provided to neurosurgeons regarding the safety and efficacy of their trajectories. In this work, we present a novel architecture specifically designed to ease the SEEG trajectory planning using the 3D Slicer platform as a basis. Trajectories are automatically optimized following criteria like vessel distance and insertion angle. Multi-trajectory optimization and conflict resolution are optimized through a selective brute force approach based on a conflict graph construction. Additionally, electrode-specific optimization constraints can be defined, and an advanced verification module allows neurosurgeons to evaluate the feasibility of the trajectory. A retrospective evaluation was performed using manually planned trajectories on 20 patients: the planning algorithm optimized and improved trajectories in 98% of cases. We were able to resolve and optimize the remaining 2% by applying electrode-specific constraints based on manual planning values. In addition, we found that the global parameters used discards 68% of the manual planned trajectories, even when they represent a safe clinical choice. Our approach improved manual planned trajectories in 98% of cases in terms of quantitative indexes, even when applying more conservative criteria with respect to actual clinical practice. The improved multi-trajectory strategy overcomes the previous work limitations and allows electrode optimization within a tolerable time span.

Laughter is a complex motor behavior that, typically, expresses mirth. Despite its fundamental role in social life, knowledge about the neural basis of laughter is very limited and mostly based on a few electrical stimulation (ES) studies carried out in epileptic patients. In these studies laughter was elicited from temporal areas where it was accompanied by mirth and from frontal areas plus an anterior cingulate case where laughter without mirth was observed. On the basis of these findings, it has been proposed a dichotomy between temporal lobe areas processing the emotional content of laughter and anterior cingulate cortex (ACC) and motor areas responsible of laughter production. The present study is aimed to understand the role of ACC in laughter. We report the effects of stimulation of 10 rostral, pregenual ACC (pACC) patients in which the ES elicited laughter. In half of the patients ES elicited a clear burst of laughter with mirth, while in the other half mirth was not evident. This large dataset allow us to offer a more reliable picture of the functional contribute of this region in laughter, and to precisely localize it in the cingulate cortex. We conclude that the pACC is involved in both the motor and the affective components of emotions, and challenge the validity of a sharp dichotomy between motor and emotional centers for laughing. Finally, we suggest a possible anatomical network for the production of positive emotional expressions.

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

Negative myoclonus (NM) is a motor disorder characterized by a sudden and abrupt interruption of muscular activity. The EMG correlate of NM is a brief (<500 ms) silent period (SP) not preceded by any enhancement of EMG activity (i.e. myoclonus). This study investigated the role of premotor cortex (PMC), primary motor cortex (MI), primary somatosensory area (SI) and supplementary motor area (SMA) in the pathophysiology of cortical NM by means of intracerebral low frequency (1 Hz) electrical stimulation. In three drug-resistant epileptic patients undergoing presurgical evaluation, we delivered single electric pulses (stimulus duration: 3 ms; stimulus intensity ranging from 0.4 to 3 mA) to PMC (2 patients), MI (1 patient), SI and SMA through stereo-EEG electrodes; surface EMG was collected from both deltoids. The results showed that (i) the stimulation of PMC or MI could evoke a motor evoked potential (MEP) either at rest or during contraction, in this latter case followed by an SP; however, in two patients, at the lowest stimulus intensities (0.4 mA), 50% of stimuli could induce a pure SP, i.e. not preceded by an MEP; raising the intensity of stimulation (0.6 mA), the SPs showed an antecedent MEP in >80% of stimuli; (ii) the stimulation of SI at low stimulus intensities (from 0.4 to 0.8 mA) induced in two patients only SPs, never associated with an antecedent MEP, whereas in the third subject the SPs could be inconstantly preceded by an MEP; by incrementing the stimulus intensity (up to 3 mA), in all three patients the SPs tended to be preceded, although not constantly, by an MEP; stimulus intensity affected SP duration (i.e. the higher the intensity, the longer the SP), without influencing the latency of onset of the SPs; (iii) the stimulation of SMA induced only pure SPs, at all stimulus intensities up to 3 mA; as for SI, increment of stimulus intensity was paralleled by an increase in SP duration, without influencing the onset latency of SPs. We conclude that single electric pulse stimulation of PMC, MI, SI and SMA through stereo-EEG electrodes can induce pure SPs, not preceded by an MEP, which clinically appear as NM, suggesting therefore that these cortical areas may be involved in the genesis of this motor phenomenon. However, it must be pointed out that SMA stimulation induced only pure SPs, regardless of the stimulus intensity, whereas occurrence of pure SPs following stimulation of PMC, MI, and SI depended mainly on the intensity of stimulation.

To show the results of the investigation conducted with intracerebral electrodes in a patient with drug-resistant nocturnal frontal lobe epilepsy, characterized by sleep-related paroxysmal motor attacks of increasing complexity ranging from simple and brief stereotyped motor events to paroxysmal arousals and major attacks.

SummaryHigh‐resolution imaging techniques can demonstrate anatomic alterations in most patients identified as candidates for surgical treatment of their partial epilepsy. The demonstration of an anatomic lesion is only one step in the presurgical diagnostic procedure, which includes video‐EEG and, when necessary, video‐stereo‐EEG recordings of seizures. A review of the literature shows that the simple removal of the magnetic resonance imaging (MRI)‐evident lesion (“lesionectomy”) reduces but does not completely suppress seizures in a large percentage of patients, especially those with neuronal migration disorders. This phenomenon could, at least in part, be explained by preliminary data (in 33 patients) showing that less than 20% of seizures correspond to a well‐localized, intra‐lesional discharge in about 40% of stereo‐EEG‐investigated patients with at least one intralesional electrode. The authors illustrate some anatomo‐electroclinical examples of intra‐individual variability of the ictal symptomatology, raising the problem of the decision about the extent of the surgical removal. Recent histologic and immunohistochemical studies have demonstrated several kinds of structural alterations in the stereo‐EEG‐defined epileptogenic zone, not always overlapping with the MRI‐visible lesion. This aspect can further explain some failures of MRI‐guided lesionectomies. That relationships between “lesions” and epileptogenic zones may be variable is also suggested by reports of patients who present with multiple lesions (i.e., cavernous angiomas, Bourneville syndrome) and are cured by removal of only one of them.

Graphical Abstract

Graphical Abstract

Our understanding of cortical alterations and related epilepsies has grown enormously in the last decade thanks to the explosion of basic information from laboratory neuroscience combined with advances in diagnostic tools, therapeutic approaches and surgical techniques. In the present paper, we briefly review the most important advances in these fields from the point of view of the clinician concerned with cortical malformation‐related epilepsies. We propose that a highly effective way forward, expected not only to widen knowledge of the basic mechanisms of seizure generation, but also to improved the management of patients, would be to promote interdisciplinary research programmes on resected human cortex that involve neurosurgeons, neurologists and laboratory neuroscientists.

To show the results of the exploration conducted with intracerebral electrodes in a patients affected by epileptic nocturnal wanderings (ENWs).