Negative MRI and a seizure onset zone close to eloquent areas in FCD type II: Application of MRg-LiTT after a SEEG re-evaluation in pediatric patients with a previous failed surgery.

OBJECTIVE: Negative MRI and an epileptogenic zone (EZ) adjacent to eloquent areas are two main issues that can be encountered during pre-surgical evaluation for epilepsy surgery. Focal Cortical Dysplasia type II (FCD type II) is the most common aetiology underlying a negative MRI. The objective of this study is to present three cases of pediatric patients exhibiting negative MRI and a seizure onset zone close to eloquent areas, who previously underwent traditional open surgery or SEEG-guided radiofrequency thermocoagulations (RF-TC). After seizure seizure recrudescence, pre-surgical SEEG was re-evaluated and Magnetic Resonance-guided laser interstitial thermal therapy (MRg-LiTT) was performed. We discuss the SEEG patterns, the planning of laser probes trajectories and the outcomes one year after the procedure. METHODS: Pediatric patients who underwent SEEG followed by MRg-LiTT for drug-resistant epilepsy associated with FCD type II at our Centre were included. Pre-surgical videoEEG (vEEG), stereoEEG (sEEG), and MRI were reviewed. Post-procedure clinical outcome (measured by Engel score) and complications rates were evaluated. RESULTS: Three patients underwent 3 MRg-LiTT procedures from January 2022 to June 2022. Epileptogenic zone was previously studied via SEEG in all the patients. All the three patients pre-surgical MRI was deemed negative. Mean age at seizure onset was 47 months (21-96 months), mean age at MRg-LiTT was 12 years (10 years 10 months - 12 years 9 months). Engel class Ia outcome was achieved in patients #2 and #3, Engel class Ib in patient #1. Mean follow-up length was of 17 months (13 months - 20 months). Complications occurred in one patient (patient #2, extradural hematoma). CONCLUSIONS: The combined use of SEEG and MRg-LiTT in complex cases can lead to good outcomes both as a rescue therapy after failed surgery, but also as an alternative to open surgery after a successful SEEG-guided Radiofrequency Thermocoagulation (RF-TC). Specific SEEG patterns and a previous good outcome from RF-TC can be predictors of a favourable outcome.

Stereo-EEG tailored resection in a child with presumed perinatal post-stroke epilepsy: The complex organization of epileptogenic zone.

Introduction: Only a few studies have focused on tailored resection in post-stroke epilepsy, in which hemispherectomy and hemispherotomy are the most recognized treatments. Case description: We describe the case of a patient with drug-resistant, presumed perinatal, post-stroke epilepsy and moderate right hemiparesis. The seizures were stereotyped, both spontaneous and induced by sudden noises and somatosensory stimuli. Considering the discordant anatomic-electro-clinical data - left perisylvian malacic lesion with electrical onset over the left mesial fronto-central leads - and the patient's functional preservation, SEEG was performed. SEEG revealed sub-continuous abnormalities in the perilesional regions. Several seizures were recorded, with onset over the premotor area, rapidly involving the motor and insular-opercular regions. We decided for a combined surgical approach, SEEG-guided radiofrequency thermocoagulation, on the fronto-mesial structure but also on the central operculum, followed by resective surgery including only the fronto-mesial structures. Discussion and conclusion: The SEEG allowed to localize the epileptogenic zone far away from the anatomical lesion but connected to part of it. A combined surgical approach tailored on SEEG results allowed a good outcome (Engel Ib) without additional deficits.

Multi-trajectories automatic planner for StereoElectroEncephaloGraphy (SEEG).

PURPOSE: StereoElectroEncephaloGraphy (SEEG) is done to identify the epileptogenic zone of the brain using several multi-lead electrodes whose positions in the brain are pre-operatively defined. Intracranial hemorrhages due to disruption of blood vessels can cause major complications of this procedure ([Formula: see text]1%). In order to increase the intervention safety, we developed and tested planning tools to assist neurosurgeons in choosing the best trajectory configuration. METHODS: An automated planning method was developed that maximizes the distance of the electrode from the vessels and avoids the sulci as entry points. The angle of the guiding screws is optimized to reduce positioning error. The planner was quantitatively and qualitatively compared with manually computed trajectories on 26 electrodes planned for three patients undergoing SEEG by four neurosurgeons. Quantitative comparison was performed computing for each trajectory using (a) the Euclidean distance from the closest vessel and (b) the incidence angle. RESULTS: Quantitative evaluation shows that automatic planned trajectories are safer in terms of distance from the closest vessel with respect to manually planned trajectories. Qualitative evaluation performed by four neurosurgeons showed that the automatically computed trajectories would have been preferred to manually computed ones in 30% of the cases and were judged good or acceptable in about 86% of the cases. A significant reduction in time required for planning was observed with the automated system (approximately 1/10). CONCLUSION: The automatic SEEG electrode planner satisfied the essential clinical requirements, by providing safe trajectories in an efficient timeframe.

Epileptic motor behaviors during sleep: anatomo-electro-clinical features.

BACKGROUND: Sleep-related complex motor seizures have long been considered pathognomonic features of Nocturnal Frontal Lobe Epilepsy (NFLE). In recent years, these manifestations have also been reported to have a temporal or insular origin. METHOD: We describe 40 drug-resistant epileptic patients with complex motor seizures during sleep, submitted to presurgical stereo-EEG (SEEG) evaluation and seizure-free after surgical resection of the epileptogenic zone. RESULTS: In a significant proportion (30%) of these patients, seizures arose from extra-frontal regions, including mainly the temporal lobe and the insular cortex, but also the parietal and occipital lobes. In patients with extra-frontal epilepsy, when complex motor behaviors appeared, SEEG revealed that the ictal discharge involved the cingulate and the frontal regions. Finally, at histology, Taylor's focal cortical dysplasia (TFCD) was the most common finding (90% of patients), independent of the site of seizure onset. CONCLUSION: As previously reported by other studies, this histologic substrate may be a major determinant of sleep-related seizures in drug-resistant epileptic patients.

Risk factors for postoperative depression in 150 subjects treated for drug-resistant focal epilepsy.

OBJECTIVE: The primary goal was to identify risk factors for post-surgical depression in subjects operated on for drug-resistant epilepsy. Secondary goals were to confirm the high rate of depression in subjects suffering from epilepsy (prior to surgery) and to look for first post-surgical depressive episode. METHODS: Case series study of 150 subjects surgically treated for partial epilepsy (side of surgery: 72 right, 78 left; site of surgery: 97 Unilobar Temporal, 17 Unilobar Frontal, 14 Posterior, 22 Multilobar). All subjects routinely had three psychiatric evaluations: before surgery (baseline) and at 6 and 12 months after surgery. Psychiatric diagnoses were made according to DSM-IV-TR criteria. Bivariate (Fisher exact test and Kruskal-Wallis rank sum test) and multivariate (logistic regression model fitting) analyses were performed. RESULTS: Thirty-three (22%) subjects had post-surgical depressive episodes, 31 of them in the first 6 months. Fourteen out of 33 experienced depression for the first time. Post-surgical depressive episodes are not associated with gender, outcome on seizures, side/site of surgical resection, histological diagnosis, psychiatric diagnoses other than depression. Depressive episodes before surgery and older age at surgery time are risk factors for post-surgical depression (p= 0.0001 and 0.01, respectively, at logistic regression analysis). No protective factors were identified. CONCLUSIONS: Our data show that lifetime depressive episodes and older age at surgery time are risk factors for postsurgery depression. Moreover, a prospective study could be useful in order to assess whether depression is really a consequence of surgery.

Surgical treatment of drug-resistant nocturnal frontal lobe epilepsy.

Of the cases with nocturnal frontal lobe epilepsy (NFLE) approximately 30% are refractory to antiepileptic medication, with several patients suffering from the effects of both ongoing seizures and disrupted sleep. From a consecutive series of 522 patients operated on for drug-resistant focal epilepsy, 21 cases (4%), whose frontal lobe seizures occurred almost exclusively (>90%) during sleep, were selected. All patients underwent a comprehensive pre-surgical evaluation, which included history, interictal EEG, scalp video-EEG monitoring, high-resolution MRI and, when indicated, invasive recording by stereo-EEG (SEEG). There were 11 males and 10 females, whose mean age at seizure onset was 6.2 years, mean age at surgery was 24.7 years and seizure frequency ranged from <20/month to >300/month. Nine patients reported excessive daytime sleepiness (EDS). Prevalent ictal clinical signs were represented by asymmetric posturing (6 cases), hyperkinetic automatisms (10 cases), combined tonic posturing and hyperkinetic automatisms (4 cases) and mimetic automatisms (1 case). All patients reported some kind of subjective manifestations. Interictal and ictal EEG provided lateralizing or localizing information in most patients. MRI was unrevealing in 10 cases and it showed a focal anatomical abnormality in one frontal lobe in 11 cases. Eighteen patients underwent a SEEG evaluation to better define the epileptogenic zone (EZ). All patients received a microsurgical resection in one frontal lobe, tailored according to pre-surgical evaluations. Two patients were operated on twice owing to poor results after the first resection. Histology demonstrated a Taylor-type focal cortical dysplasia (FCD) in 16 patients and an architectural FCD in 4. In one case no histological change was found. After a post-operative follow-up of at least 12 months (mean 42.5 months) all the 16 patients with a Taylor's FCD were in Engel's Class Ia and the other 5 patients were in Engel's Classes II or III. After 6 months post-surgery EDS had disappeared in the 9 patients who presented this complaint pre-operatively. It is concluded that patients with drug-resistant, disabling sleep-related seizures of frontal lobe origin should be considered for resective surgery, which may provide excellent results both on seizures and on epilepsy-related sleep disturbances. An accurate pre-surgical evaluation, which often requires invasive EEG recording, is mandatory to define the EZ. Further investigation is needed to explain the possible causal relationships between FCD, particularly Taylor-type, and sleep-related seizures, as observed in this cohort of NFLE patients.

Electroclinical, MRI and neuropathological study of 10 patients with nodular heterotopia, with surgical outcomes.

We present the results of a retrospective study on 10 patients operated on for intractable epilepsy associated with nodular heterotopia as identified by high resolution MRI. Seven patients had unilateral heterotopia, one patient had symmetric bilateral heterotopia and two patients had asymmetric bilateral heterotopia. By stereo-electroencephalogram (SEEG) (nine patients) interictal activity within nodules was similar in all cases, and ictal activity never started from nodules alone but from the overlying cortex or simultaneously in nodules and cortex. Excellent outcomes (Engel class Ia, 1987) were achieved in the seven patients with unilateral heterotopia, showing that surgery can be highly beneficial in such cases when the epileptogenic zone is carefully located prior to surgery by MRI and particularly SEEG. For the bilateral cases surgical outcomes were Engel IIa (one patient) or Engel IIIa (two patients). Histological/immunohistochemical studies of resected specimens showed that all nodules had similar microscopic organization, even though their extent and location varied markedly. The overlying cortex was dysplastic in nine patients, but of normal thickness. We suggest that nodule formation may be the result of a dual mechanism: (i) failure of a stop signal in the germinal periventricular region leading to cell overproduction; and (ii) early transformation of radial glial cells into astrocytes resulting in defective neuronal migration. The intrinsic interictal epileptiform activity of nodules may be due to an impaired intranodular GABAergic system.

Surgery for drug resistant partial epilepsy in children with focal cortical dysplasia: anatomical-clinical correlations and neurophysiological data in 10 patients.

OBJECTIVE: To analyse a population of children with focal cortical dysplasia operated on for drug resistant partial epilepsy, with emphasis on clinical features, seizure semiology, interictal and ictal EEG and stereo EEG findings, histological and topographical characteristics of the lesions, extension and localisation of cerebral excision, and its postoperative effect on seizure frequency. METHODS: 10 patients were studied, aged between 26 months and 11 years (median 6 years). Magnetic resonance imaging (MRI) abnormalities were unilobar (temporal 3, frontal 2), bilobar (2), or multilobar (1); the two patients with negative MRI suffered from frontal seizures. Presurgical diagnostic steps varied in complexity and invasiveness depending on the anatomical/electrical/clinical features of each patient. In four patients they included only scalp video EEG monitoring, and in six, also invasive recordings using stereotactically implanted intracerebral electrodes. Surgery consisted of corticectomy plus lesionectomy in all cases. RESULTS: 70% of the patients were seizure-free after a minimum postoperative follow up of 25 months. These included three patients with temporal lesions and four of seven patients with other lobar or multilobar extratemporal localisation. One patient had improvement in seizure control. Outcome was poor in multilobar patients, but a class Ia outcome was obtained in one case after partial lesionectomy associated with bilobar corticectomy. All patients showed developmental improvement. CONCLUSIONS: Analysis of the data in these patients allowed the production of an "anatomical-clinical concordance" list, which appeared to be correlated with the diagnostic steps performed. Carrying out a stereo EEG exploration in the most complex cases proved useful in defining the epileptogenic zone in extratemporal and multilobar epilepsies. Stereo EEG recordings facilitated a tailored resection of extralesional cortex.

A neuropathological, stereo-EEG, and MRI study of subcortical band heterotopia.

The authors performed an MRI, stereo-EEG, and pathology study on a woman with subcortical band heterotopia and partial epilepsy. Clinical manifestations of seizures always started when ictal discharges were present in outer and heterotopic cortices. Simultaneous activation of both cortices and presence of differentiated neurons in the white matter and the heterotopia strongly suggest that the cortices were anatomically and functionally interconnected.

Focal cortical dysplasia: neuropathological subtypes, EEG, neuroimaging and surgical outcome.

Since the original description by Taylor, the term focal cortical dysplasia has been used to refer to a wide range of alterations of the cortical mantle. More recently, these conditions have been described from neuroimaging, neuropathological and genetic standpoints, generating several classifications. It is widely recognized that these classifications are unsatisfactory. We propose a simplified classification of focal cortical dysplasias based on easily recognized neuropathological characteristics. We retrospectively re-examined histological sections of cortex from 52 of 224 (23%) patients operated on for drug-resistant partial epilepsy in which cortical dysplasia was present but not associated with other brain pathologies except hippocampal sclerosis. Three subgroups were identified: (i) architectural dysplasia (31 patients) characterized by abnormal cortical lamination and ectopic neurones in white matter; (ii) cytoarchitectural dysplasia (six patients) characterized by giant neurofilament-enriched neurones in addition to altered cortical lamination; and (iii) Taylor-type cortical dysplasia (15 patients) with giant dysmorphic neurones and balloon cells (all but two patients) associated with cortical laminar disruption. The patients with architectural dysplasia had lower seizure frequency than those with cytoarchitectural and Taylor-type dysplasia, and the epileptogenic zone was mainly in the temporal lobe. In patients with Taylor-type dysplasia, the epileptogenic zone was mainly extratemporal, and interictal stereo-EEG was distinctive. MRI was unrevealing in 34% of patients, but distinctive signal alterations characterized most patients with Taylor-type dysplasia, while focal hypoplasia with MRI abnormalities was found in architectural dysplasia. Patients with Taylor-type dysplasia had the best outcome, with 75% seizure-free (Engel class Ia) after at least a year of follow-up compared with 50% of cytoarchitectural dysplasia and 43% of architectural dysplasia patients seizure-free. This three-category classification is based on easily recognized histopathological characteristics and avoids complicated terminology, while the distinctive ensemble of other characteristics defines clinically homogeneous groups.

Clinical ictal symptomatology and anatomical lesions: their relationships in severe partial epilepsy.

High-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 ("lesion-ectomy") 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, intralesional discharge in about 40% of stereo-EEG-investigated patients with at least one intralesional electrode. The authors illustrate some anatomo-electroclinical examples of intraindividual 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.

Presurgical strategies and epilepsy surgery in children: comparison of literature and personal experiences.

We reviewed 41 studies on epilepsy surgery in 1645 children and adolescents. The available data vary greatly from one paper to another, particularly as regards the age of the patients included, selection criteria, presurgical methodology, and the type of surgical intervention. Moreover, the surgical results are classified according to very different criteria. Our experience in Grenoble concerning 55 children (age < or = 16 years; postoperative follow-up > 18 months) is discussed in the light of data in the literature. The need is stressed for a consensus on the type of information that must be supplied by well-detailed studies on homogeneous groups of epilepsy surgery patients.

Research perspectives in cortical dysplasia and associated epilepsies.

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.

[Relationship between anatomic lesions of the temporal lobe and temporal lobe epilepsy]. / Relazioni tra lesione anatomica temporale e tipo di epilessia.

A structural lesion of the brain is a frequent finding in intractable partial epileptic patients. We analyse anatomo-electro-clinical characteristics of 58 patients in which MR showed a lesion inside the temporal lobe. They are 29 males and 29 females with a mean age at surgery of 23.5 +/- 10.7 years (2.6-45.9). The mean epilepsy duration is of 13.4 +/- 8 years (1.3-35.5), with a mean seizure frequency of 28.7 +/- 43.6 per month, with a great inter-individual variability (from 3 per month to 15 a day). The minimum follow-up is 3.5 years. A video-EEG monitoring was performed in 21 cases, while a stereo-EEG investigation was judged mandatory in 26. On the basis of anatomo-electro-clinical correlations and of the results of presurgical investigations, the epileptogenic area was proved to be temporal in 49 cases, temporal but controlateral to the lesion in 1, and at least bilobar in 8 patients.

[Surgical treatment of temporal lobe epilepsy: reality and prospectives]. / Trattamento chirurgico delle epilessie temporali: realtà e prospettive.

This chapter provides a synthetic overview of the topics treated in this issue. Presurgical diagnostic procedures are schematically described and an analysis of surgical results is made in comparison with those obtained from other epilepsy surgery groups. Surgical complications linked both to invasive presurgical diagnostic procedures and therapeutic surgical acts are described. Finally, the creation of new epilepsy surgery centres is suggested on the basis of epidemiological data, which demonstrate the discrepancy among the patients operated on at present and those who could benefit from the surgical treatment.

[Characteristics of the global population]. / Caratteristiche della popolazione globale analizzata.

We analyse clinical characteristics, presurgical investigations, surgical procedures and outcome of 137 patients operated-on for a drug-resistant partial epilepsy, in Grenoble from January 1990 to December 1993. Moreover we present data of 63 patients suffering from a "pure" temporal lobe epilepsy selected using the following criteria: 1. surgery limited to temporal lobe structures 2. totally cured after surgery (Engel's class la).

Role of the hypothalamic hamartoma in the genesis of gelastic fits (a video-stereo-EEG study).

Patients having a hypothalamic hamartoma frequently present epileptic attacks of laughter, and they later experience multiple additional seizure types, which invariably lead to a severe drug-resistant epilepsy. If this association is now well-known, relationships between the hypothalamic mass and the different types of seizures remain still mysterious. We report the case of a 16-year-old girl suffering from this peculiar epileptic picture, in whom a stereo-EEG study was performed, allowing us to record both the hamartoma, the neighboring hypothalamic structures, and other bilateral cortical areas. It showed that gelastic fits were strictly linked to ictal discharges which began and remained well localized in the hamartoma. Conversely, atonic seizures, which might result from a secondary epileptogenesis, admitted a widely extended bilateral frontal cortical origin, sparing the lesion, and slightly involving the posterior hypothalamus. Stereotactic radiosurgery of the hamartoma proved to be ineffective on both types of seizures, probably because of the too low dose of X-rays delivered (18 grays), as suggested by the absence of hypothalamic mass changes on MRI. Such data, never reported to our knowledge, seem able to contribute to a better understanding of this very peculiar epileptic syndrome, and perhaps to a better adapted therapeutic management.

Stereo-EEG of interictal and ictal electrical activity of a histologically proved heterotopic gray matter associated with partial epilepsy.

Magnetic resonance imaging allows the identification of heterotopic gray matter (HGM) in medically intractable partial epilepsies. The relationships between HGM and the epileptogenic zone remain, however, unclear. In a case of a temporo-parietal epilepsy studied by stereo-EEG, interictal and ictal electrical activity of a temporal HGM were recorded, showing: (1) an intralesional electrical activity, (2) the possible presence of asynchronous spikes, and (3) an early but never initial, or isolated, involvement during ictal discharges. This suggests that the presurgical and surgical management of HGM must be guided, as for other lesions, by the coherence existing between ictal clinical and electrical features, and anatomical data.

Stereo-electroencephalography methodology: advantages and limits.

Since January 1990, 70 patients with medically intractable partial epilepsy underwent a stereo-EEG investigation in our center. We first described technical requirements, and gave an overview of the variety of the explored cerebral regions and implantation patterns realized, pointing out the low rate of morbidity (1.4%). The three-dimensional epileptogenic zone thus defined led to a tailored individualized surgical excision in 60 patients, while 9 are waiting for surgery and the remaining 1 has been excluded (1.4%). Conceptual and technical aspects of the stereo-EEG methodology were discussed in order to underline its peculiarities in the field of "depth recordings", and more generally among the broader group of "invasive" procedures.