Genetic Insights Into Hypothalamic Hamartoma: Unraveling Somatic Variants.

Objectives: Hypothalamic hamartomas (HHs) are rare developmental brain lesions associated with drug-resistant epilepsy and often subjected to epilepsy surgery. Brain somatic variants in genes affecting the Sonic hedgehog (Shh) and primary cilia signaling pathways have been implicated in approximately 50% of nonsyndromic HH cases. This study aims to characterize a new cohort of 9 HH cases and elucidate their genetic etiology. Methods: We recruited 9 HH cases including 8 nonsyndromic cases of which 4 were type IV HH. Genomic DNA was extracted from peripheral blood and surgical brain tissues, and somatic variants were investigated using high-depth whole-exome sequencing. Results: Pathogenic somatic variants in known HH genes (GLI3, OFD1, and PRKACA) were identified in 7 of the 9 cases. In addition, a 2-hit mutational event comprising a germline variant (predicted to impair kinase activity) and a somatic loss-of-heterozygosity was identified in TNK2, a gene encoding a brain-expressed tyrosine kinase. Discussion: Our findings reinforce the role of somatic variants in Shh and cilia genes in HH cases while also shedding light on TNK2 as a potential novel disease-causing gene. This study emphasizes the increasing importance of brain mosaicism in epilepsy disorders and underscores the critical role of genetic diagnosis derived from resected brain tissue.

Stereoelectroencephalography-guided radiofrequency thermocoagulation.

Within the neurosurgeon's armamentarium, stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC) is an elegant tool to manage epilepsy in selected cases. This technique can 1) be curative when targeting small-volume ictal onset zones, 2) be used as a diagnostic tool by observing the consequences of coagulation on seizures or by recording the epileptic network in SEEG, and 3) offer palliative treatment through multiple lesions within a wide epileptic network. It is performed on awake patients, under continuous neurological evaluation, while monitoring impedance, time, and energy delivered. It could offer highly favorable outcomes in some cases, as in periventricular nodular heterotopia where 81% of patients are responders.

Insights on cognitive reorganization after hemispherectomy in Rasmussen's encephalitis. A narrative review.

Rasmussen's encephalitis is a rare neurological pathology affecting one cerebral hemisphere, therefore, posing unique challenges. Patients may undergo hemispherectomy, a surgical procedure after which cognitive development occurs in the isolated contralateral hemisphere. This rare situation provides an excellent opportunity to evaluate brain plasticity and cognitive recovery at a hemispheric level. This literature review synthesizes the existing body of research on cognitive recovery following hemispherectomy in Rasmussen patients, considering cognitive domains and modulatory factors that influence cognitive outcomes. While language function has traditionally been the focus of postoperative assessments, there is a growing acknowledgment of the need to broaden the scope of language investigation in interaction with other cognitive domains and to consider cognitive scaffolding in development and recovery. By synthesizing findings reported in the literature, we delineate how language functions may find support from the right hemisphere after left hemispherectomy, but also how, beyond language, global cognitive functioning is affected. We highlight the critical influence of several factors on postoperative cognitive outcomes, including the timing of hemispherectomy and the baseline preoperative cognitive status, pointing to early surgical intervention as predictive of better cognitive outcomes. However, further specific studies are needed to confirm this correlation. This review aims to emphasize a better understanding of mechanisms underlying hemispheric specialization and plasticity in humans, which are particularly important for both clinical and research advancements. This narrative review underscores the need for an integrative approach based on cognitive scaffolding to provide a comprehensive understanding of mechanisms underlying the reorganization in Rasmussen patients after hemispherectomy.

Targeting pathological cells with senolytic drugs reduces seizures in neurodevelopmental mTOR-related epilepsy.

Cortical malformations such as focal cortical dysplasia type II (FCDII) are associated with pediatric drug-resistant epilepsy that necessitates neurosurgery. FCDII results from somatic mosaicism due to post-zygotic mutations in genes of the PI3K-AKT-mTOR pathway, which produce a subset of dysmorphic cells clustered within healthy brain tissue. Here we show a correlation between epileptiform activity in acute cortical slices obtained from human surgical FCDII brain tissues and the density of dysmorphic neurons. We uncovered multiple signatures of cellular senescence in these pathological cells, including p53/p16 expression, SASP expression and senescence-associated ß-galactosidase activity. We also show that administration of senolytic drugs (dasatinib/quercetin) decreases the load of senescent cells and reduces seizure frequency in an MtorS2215F FCDII preclinical mouse model, providing proof of concept that senotherapy may be a useful approach to control seizures. These findings pave the way for therapeutic strategies selectively targeting mutated senescent cells in FCDII brain tissue.

Functional hemispheric disconnection procedures for chronic epilepsy: history, indications, techniques, complications and current practice in Europe. A consensus statement on behalf of the EANS functional neurosurgery section.

Introduction: The surgical procedure for severe, drug-resistant, unilateral hemispheric epilepsy is challenging. Over the last decades the surgical landscape for hemispheric disconnection procedures changed from anatomical hemispherectomy to functional hemispherotomy with a reduction of complications and stable good seizure outcome. Here, a task force of European epilepsy surgeons prepared, on behalf of the EANS Section for Functional Neurosurgery, a consensus statement on different aspects of the hemispheric disconnection procedure. Research question: To determine history, indication, timing, techniques, complications and current practice in Europe for hemispheric disconnection procedures in drug-resistant epilepsy. Material and methods: Relevant literature on the topic was collected by a literature search based on the PRISMA 2020 guidelines. Results: A comprehensive overview on the historical development of hemispheric disconnection procedures for epilepsy is presented, while discussing indications, timing, surgical techniques and complications. Current practice for this procedure in European epilepsy surgery centers is provided. At present, our knowledge of long-term seizure outcomes primarily stems from open surgical disconnection procedures. Although minimal invasive surgical techniques in epilepsy are rapidly developing and reported in case reports or small case series, long-term seizure outcome remain uncertain and needs to be reported. Discussion and conclusion: This is the first paper presenting a European consensus statement regarding history, indications, techniques and complications of hemispheric disconnection procedures for different causes of chronic, drug-resistant epilepsy. Furthermore, it serves as the pioneering document to report a comprehensive overview of the current surgical practices regarding this type of surgery employed in renowned epilepsy surgery centers across Europe.

Deep retroinsular and parieto-opercular origin of vestibular symptoms: A stereoelectrocenphalography (SEEG) study.

Several studies have shown that the retroinsular and posterior parietal operculum regions play a central role in vestibular processing. Electrical stimulations performed during stereoelectroencephalography (SEEG) in patients with focal drug-resistant epilepsy could contribute to the analysis of this area. Among the 264 SEEGs performed in both an adult and a paediatric epilepsy surgery centre, we retrospectively identified 24 patients (9%) reporting vertigo during electrical stimulations (ES). In seven of them (29% of patients experiencing vertigo during ES), it was evoked by stimulating the retroinsular region. The reported responses were mostly not rotatory sensations but actually illusions of body, limb or limb segment movement. The involved area is limited. Moreover, two patients reported having the same symptoms at the beginning of their seizures starting in the same region. Our case study confirms the pivotal role of the retroinsular and posterior parietal operculum areas in vestibular responses, and we therefore advise the exploration of this region when patients report an illusion of body movement at the beginning of their seizures.

Detection of brain somatic mutations in focal cortical dysplasia during epilepsy presurgical workup.

Brain-restricted somatic variants in genes of the mechanistic target of rapamycin signalling pathway cause focal epilepsies associated with focal cortical dysplasia type II. We hypothesized that somatic variants could be identified from trace tissue adherent to explanted stereoelectroencephalography electrodes used in the presurgical epilepsy workup to localize the epileptogenic zone. We investigated three paediatric patients with drug-resistant focal epilepsy subjected to neurosurgery. In the resected brain tissue, we identified low-level mosaic somatic mutations in AKT3 and DEPDC5 genes. We collected stereoelectroencephalography depth electrodes in the context of a second presurgical evaluation and identified 4/33 mutation-positive electrodes that were either located in the epileptogenic zone or at the border of the dysplasia. We provide the proof-of-concept that somatic mutations with low levels of mosaicism can be detected from individual stereoelectroencephalography electrodes and support a link between the mutation load and the epileptic activity. Our findings emphasize future opportunities for integrating genetic testing from stereoelectroencephalography electrodes into the presurgical evaluation of refractory epilepsy patients with focal cortical dysplasia type II to improve the patients' diagnostic journey and guide towards precision medicine.

Cognitive outcome after left functional hemispherectomy on dominant hemisphere in patients with Rasmussen encephalitis: beyond the myth of aphasia. Patient series.

BACKGROUND: Rasmussen encephalitis is a rare chronic neurological pathology frequently treated with functional hemispherectomy (or hemispherotomy). This surgical procedure frees patients of their severe epilepsy associated with the disease but may induce cognitive disorders and notably language alterations after disconnection of the left hemisphere. OBSERVATIONS: The authors describe longitudinally 3 cases of female patients with Rasmussen encephalitis who underwent left hemispherotomy in childhood and benefited from a favorable cognitive outcome. In the first patient, the hemispherotomy occurred at a young age, and the recovery of language and cognitive abilities was rapid and efficient. The second patient benefited from the surgery later in childhood. In addition, she presented a reorganization of language and memory functions that seem to have been at the expense of nonverbal ones. The third patient was a teenager during surgery. She benefited from a more partial cognitive recovery with persistent disorders several years after the surgery. LESSONS: Recovery of cognitive functions, including language, occurs after left hemispherotomy, even when performed late in childhood. Therefore, the surgery should be considered as early as possible to promote intercognitive reorganization.

Preservation of frontal white matter tracts in ventricular surgery: favoring an anterior interhemispheric transcallosal approach vs a transcortical transfrontal transventricular approach.

Secondary to the creation of a surgical corridor and retraction, white matter tracts degenerate, causing long-term scarring with potential neurological consequences. Third and lateral ventricle tumors require surgery that may lead to cognitive impairment. Our objective is to compare the long-term consequences of a transcortical transfrontal approach and an interhemispheric transcallosal approach on corpus callosum and frontal white matter tracts degeneration. Surgical patients with ventricular tumor accessible through both approaches were included and clinico-radiological data were retrospectively analyzed. The primary endpoint was the callosotomy length at 3-month post-operative T1 MRI, corrected by the extension of the tumor and the use of neuronavigation. Secondary outcomes included perioperative criteria such as bleeding, use of retractors and duration, FLAIR hypersignal on 3-month MRI, and re-do surgeries. To assess white matter tract interruption, 3-month FLAIR hypersignal was superposed to a tractography atlas. Seventy patients were included, 57 (81%) in the transfrontal group and 13 (19%) in the interhemispheric group. There was no difference in the mean callosotomy length on 3-month MRI (12.3 mm ± 5.60 transfrontal vs 11.7 mm ± 3.92 interhemispheric, p = 0.79) on univariate and multivariate analyses. The callosotomy length was inferior by - 3.13 mm for tumors located exclusively in the third ventricle (p = 0.016), independent of the approach. Retractors were used more often in transfrontal approaches (60% vs 33%, p < 0.001). The extent of frontal FLAIR hypersignal was higher after transfrontal approach (14.1 mm vs 0.525 mm, p < 0.001), correlated to the use of retractors (p < 0.05). After the interhemispheric approach, no tract other than corpus callosum was interrupted, whereas, after the transfrontal approach, frontal arcuate fibers and projections from the thalamus were interrupted in all patients, the cingulum in 19 (33%), the superior fronto-occipital fasciculus in 15 (26%), and the superior longitudinal fasciculus in 2 (3%). Transfrontal and interhemispheric approaches to the third and lateral ventricles both lead to the same long-term damage to the corpus callosum, but the transfrontal approach interrupts several white matter tracts essential to cognitive tasks such as attention and planning, even in the non-dominant hemisphere. These results encourage all neurosurgeons to be familiar with both approaches and favor the interhemispheric approach when both can give access to the tumor with a comparable risk. Neuropsychological studies are necessary to correlate these anatomical findings to cognitive outcomes.

Hypothalamic hamartoma associated with polymicrogyria and periventricular nodular heterotopia in children: report of three cases and discussion of the origin of the seizures.

PURPOSE: Hypothalamic hamartomas (HH) are malformations responsible for drug-resistant epilepsy. HH are usually isolated or part of a genetic syndrome, such as Pallister-Hall. Exceptionally they can be associated with other brain malformations such as polymicrogyria (PMG) and periventricular nodular heterotopia (PNH). We discuss the origin of the seizures associated with this combination of malformations, through electrophysiological studies, and review the literature on this rarely reported syndrome. METHODS: We retrospectively reviewed the patients with HH who had surgery between 1998 and 2020 and selected those with associated focal PMG and PNH, detected on MRIs. All patients had comprehensive clinical evaluation and surface video-EEG and one underwent stereoelectroencephalography (SEEG). RESULTS: Three male patients out of 182 were identified with a mean age at surgery of 7.5 years. MRI showed unilateral focal PMG (fronto-insulo-parietal, fronto-insulo-parieto-opercular, and fronto-insular, respectively) and multiple PNH homolateral to the main HH implantation side. In two patients, there were strong clinical and scalp EEG arguments for seizure onset within the HH. In the third, due to abnormalities on scalp video-EEG in the same area as PMG and the lack of gelastic seizures, SEEG was indicated and demonstrated seizure onset within the hamartoma. With a mean follow-up of 6 years, two patients were seizure-free. CONCLUSION: Our results show that HH is the trigger of epilepsy, which confirms the high epileptogenic potential of this malformation. In patients such as ours, as in those with isolated HH, we recommend to begin by operating the HH independently of seizure semiology or electrophysiological abnormalities.

Complete callosotomy in children with drop attacks; A retrospective monocentric study of 50 patients.

PURPOSE: Corpus callosotomy is a palliative surgical procedure for patients with drug-resistant epilepsy and suffering from drop attacks, which are a source of major deterioration in quality of life and can be responsible for severe traumatic injury. The objective of this study is to identify clinical markers that would predict a better outcome in terms of drop attacks and other types of epileptic seizures. METHODS: We reviewed a retrospective series of children who underwent complete corpus callosotomy at our institution, between January 1998 and February 2019. We analyzed the neurological and cognitive pre- and postoperative status, radiological datas, and electroencephalography (EEG) monitoring data. RESULTS: Fifty children underwent a complete callosotomy at a mean age of 7.5 years. The median postoperative follow-up was 42.5 months. Forty-one patients (82%) had a favorable outcome, 29 (58%) of them becoming totally free of drop attacks. Statistical analysis of correlation between outcome of drop attacks and the characteristics of the patients did not find any trend in terms of age, etiology or developmental level. Regarding seizure types, the probability of being drop attack-free was significantly higher in case of tonic seizures (p = 0.017). Neurological complications occurred in two patients. A transient disconnection syndrome was observed in one child with good preoperative cognitive level. The mean hospital stay was short (5 -10 days). CONCLUSION: The results of this large monocentric case series with a long follow-up indicate that total callosotomy is a safe and effective treatment for children with drug-resistant epileptic drop attacks. Aside from a better surgical outcome for children with tonic seizures causing the falls, the lack of any other significant prognostic factor implies that no patient should a priori be excluded from this palliative surgical indication.

Vertical parasagittal hemispherotomy: a case report of postoperative mesio-temporal seizures via amygdalofugal pathway.

Vertical parasagittal hemispherotomy (VPH) is a well-established surgical treatment which is proposed for children with widespread unilateral onset of intractable epileptic seizures. VPH allows to disconnect from a vertical transventricular approach all white matter fibers of the hemisphere around a central core including the thalamus. We present the case of a girl who underwent VPH for hemimegalencephaly in early infancy. Postoperatively, she developed unexpected seizures of mesio-temporal origin. Stereo-EEG provided arguments for an amygdalar origin. High-resolution MRI with tractography confirmed the presence of the amygdalo-fugal pathway to be responsible of epileptic discharges propagation. She became seizure-free after temporal resection.

Clinical semiology of temporal lobe seizures in preschool children: contribution of invasive recording to anatomical classification.

Focal seizure semiology is often inadequately studied, specifically in preschool children. Among drug-resistant epilepsies amenable to surgery, temporal lobe seizure semiology has been widely described in this age group. Nevertheless, a systematic anatomo-electroclinical study has never been performed. We retrospectively reviewed the charts of patients younger than six years old at the time of video-EEG recording who were operated on for temporal lobe epilepsy in our centre between 2010 and 2016. In order to describe the electroclinical semiology and establish anatomo-clinical correlations, we reviewed all the recorded seizures on scalp and invasive video-EEG and analysed pre- and postsurgical clinical data, MRI scans, and surgical and pathological data. We classified patients into the following four anatomical groups: mesio-temporal, temporal lateral, polar, and mesio-lateral, and for each group we selected video-EEG samples for educational purposes. Twenty-eight patients fulfilled the selection criteria. Twenty-three patients (82%) were explored with invasive electrodes that consisted of foramen ovale electrodes in 11 (39%) and stereoelectroencephalography in 12 (43%). The majority of the 53% of patients with mesio-temporal epilepsies had specific ictal semiology, as described in adults. The others had subtle seizures or seizures limited to apnoea. The other groups also had some features comparable to adults, although no child reported the classic auras of lateral epilepsies. In total, 11% had infantile spasms (IS); post-ictal examination provided lateralization signs in 28%. With a mean post-surgical follow-up duration of 5.5 years, 89% of the patients were classified as Engel Class I. Preschool children were shown to have non-specific seizures, notably subtle events or IS. However, careful video-EEG analysis can provide arguments for localizing the epileptogenic zone within the temporal lobe in most cases. Seizures with apnoea are characteristic of mesial temporal onset in patients with long-term epilepsy-associated tumours.

18 F-FDG-PET hypometabolic pattern reveals multifocal epileptic foci despite limited unique stereotyped seizures.

PURPOSE: Interictal positron emission tomography (PET) with 18F-FDG has largely proved its utility in presurgical evaluation of drug-resistant epilepsies (DRE) and in the surgical outcomes. Interictal hypometabolism topography is related to the neuronal networks involved in the seizure onset zone (SOZ) and spread pathways. 18F-FDG PET has a good prognostic value for post-surgical outcome, especially in cases with unique focal ictal semiology and a limited extent of hypometabolism. Surprisingly few patients have similar limited ictal features but extended hypometabolism. The objective of this study is to show that stereoelectro encephalography (SEEG) provides an explanation for this large hypometabolism, which impacts the surgical strategy. METHODS: A cohort of 248 patients underwent 18F-FDG PET and SEEG to explore for refractory epilepsy in two close tertiary epilepsy centers between January 2009 and December 2017. From this cohort, a subset of patients was selected with extended PET metabolism despite showing unique and limited ictal features in scalp EEG. The surgical outcome of this subset of patients has been analysed with respect to their FDG-PET and SEEG to understand the relationship between PET/SEEG/ presentation and surgical outcome. RESULTS: We report a series of seven patients with DRE and unique stereotyped ictal semiology but extensive 18F-FDG-PET hypometabolism revealing unexpected multifocal SOZ using SEEG. All SOZ were encompassed by the hypometabolic area. CONCLUSION: Our results demonstrate the necessity of accounting for the discrepancy between limited symptoms and widespread hypometabolism which can reveal multifocal SOZ. In those patients, surgical possibilities should be considered carefully.

Focal polymicrogyria in children: Contribution of invasive explorations and epileptogenicity mapping in the surgical decision.

OBJECTIVE: Report of the contribution of invasive EEG (iEEG) and epileptogenicity mappings (EM) in a pediatric cohort of patients with epilepsy associated with focal polymicrogyria (PMG) and candidates for resective surgery. METHOD: Retrospective pediatric case series of patients presenting focal PMG-related refractory epilepsy undergoing an invasive exploration (iEEG) at Fondation Rothschild Hospital. We reviewed clinical data, structural MRI, and visual analysis of iEEG recordings. Moreover, time-frequency analysis of SEEG signals with a neuroimaging approach (epileptogenicity maps) was used to support visual analysis. RESULTS: Between 2012 and 2019, eight patients were selected. Five patients were explored with stereoelectroencephalography (SEEG) only, one patient with subdural exploration (SDE) only and two patients first underwent SEEG and then SDE. The mean age at seizure onset was 40.3 months (range 3-120), and the mean age for the iEEG 10.8 years (range 7-15). The epileptogenic zone (EZ) appeared concordant to the PMG lesion in only one case, was larger in three cases, smaller in two cases and different in one case. Four cases were selected for tailored resective surgery and one for total callosotomy. Two patients remained seizure-free at their last follow-up (mean 32.6 months, range 7-98). Epileptogenicity mapping (EM) refined the qualitative analysis, showing in four patients an EZ larger than visually defined. CONCLUSION: This study is the first pediatric study to analyze the value of iEEG and EM as well as operability in focal PMG-related refractory epilepsy. The results illustrate the complexity of this pathology with variable concordance between the EZ and the lesion and mixed response to surgery.

Management and results of epilepsy surgery associated with acyclovir prophylaxis in four pediatric patients with drug-resistant epilepsy due to herpetic encephalitis and review of the literature.

PURPOSE: Herpes simplex virus encephalitis (HSE) is the most common cause of sporadic viral encephalitis in children and is responsible for epilepsy in approximately half of patients. In addition to medical treatment, epilepsy surgery may be offered to drug-resistant patients but carries a high risk of relapse of herpetic encephalitis. We are reporting our series of patients operated on between 2000 and 2019 with the systematic administration of acyclovir (ACV). RESULTS: Four pediatric patients aged 4.5-12.8 years with drug-resistant epilepsy post-HSE underwent a tailored focal resection following invasive recordings (three patients) and a complete callosotomy (one patient). The total number of the surgical procedures for the four patients was eight, and a systematic administration of ACV as a prophylactic treatment of herpetic encephalitis relapse was done at each step. No patients had a relapse and the ACV was well-tolerated in all the cases. Following surgery two patients are seizure free, the patient who underwent callosotomy is Engel 3 and the fourth patient, in whom a large epileptic zone has contraindicated a second surgery, is Engel 4. CONCLUSIONS: Our series demonstrated the dramatic efficacy of systematic ACV prophylaxis during all cranial surgeries. Moreover, our results on epilepsy, together with those of the literature, encourage more consideration regarding epilepsy surgery in this specific etiology. All types of surgical procedures (curative or palliative) can be offered to the patients, but in the case of focal surgery, due to the poor anatomical limits, invasive recordings are highly recommended.

Seizure outcome and prognostic factors for surgical management of hypothalamic hamartomas in children.

PURPOSE: Hypothalamic hamartomas (HH) are rare benign lesions frequently associated with gelastic seizures early in life. Epilepsy can progress to multiple seizure types with cognitive impairment and behavioural disturbance, leading in some cases to epileptic encephalopathy. METHODS: We reviewed a retrospective series of 112 children treated in a single center, between 1998 and 2017. RESULTS: According to Delalande's HH classification, type1 was found in 2 patients, type 2 in 67, type 3 in 31, and type 4 in 12 patients. Stereotactic endoscopic disconnection was performed in 92 % of the procedures. Median age at diagnosis was 40 months and 7.6 years at surgery. Median time between diagnosis and surgery was 31 months and median follow up 4.1 years. For all HH types, 77.6 % of the patients had a favourable outcome (Engel I + II outcome score) with 57.1 % seizure-free (Engel I). The best outcome was obtained in patients with type 2 HH, (68.7 % Engel I and 85.1 % Engel I + II). The overall complication rate was 8.3 %, which is in line with previous series. Patients with isolated gelastic seizures had a better outcome (Engel I + II in 90 %), as compared to those with other seizure types (p = 0.07). A short delay between hamartoma diagnosis and surgery was a statistically significant factor for a good outcome (p = 0.03). CONCLUSION: Patients with HH and drug-resistant epilepsy should be early identified in order to propose surgical treatment without delay. Endoscopic disconnection is a safe and efficacious surgical option with good seizure outcome and immediate treatment results.

Invasive evaluation in children (SEEG vs subdural grids).

Designed from the 60s to the 80s for adults, and despite the development of many new techniques, invasive explorations still have indications in children with focal drug-resistant epilepsy. The main types are stereoelectroencephalography (SEEG) and subdural explorations (SDE). They provide precise information on the localization of the epileptogenic zone (EZ), its relationships with eloquent cortex, and the feasibility of performing a tailored surgical resection. Thermocoagulations, which are a diagnostic and therapeutic tool, can be performed using SEEG electrodes. Both techniques are feasible in children, with an age limitation for SEEG (which requires a bone thickness above 2 mm). The complication rate is higher with SDE. Opposed for a long time and never compared in a systematic study, they should presently be considered complementary. The indications cannot be directly inferred from those for adults, as there are pediatric particularities in the seizures' semiology, functional areas, imaging and urgent situations. We successively discuss the choice in individual cases of SEEG or SDE respectively, the specific problematic in infancy and early childhood, the schema in SEEG for cryptogenic epilepsies (in particular insular), the particularities of polymicrogyria and deeply located lesions, and finally, SEEG designed for thermocoagulations. Future improvements should include more accurate implantation schemas thanks to advanced non-invasive explorations and possibilities to perform SEEG in infants.