NeoCoMM: A neocortical neuroinspired computational model for the reconstruction and simulation of epileptiform events.

BACKGROUND: Understanding the pathophysiological dynamics that underline Interictal Epileptiform Events (IEEs) such as epileptic spikes, spike-and-waves or High-Frequency Oscillations (HFOs) is of major importance in the context of neocortical refractory epilepsy, as it paves the way for the development of novel therapies. Typically, these events are detected in Local Field Potential (LFP) recordings obtained through depth electrodes during pre-surgical investigations. Although essential, the underlying pathophysiological mechanisms for the generation of these epileptic neuromarkers remain unclear. The aim of this paper is to propose a novel neurophysiologically relevant reconstruction of the neocortical microcircuitry in the context of epilepsy. This reconstruction intends to facilitate the analysis of a comprehensive set of parameters encompassing physiological, morphological, and biophysical aspects that directly impact the generation and recording of different IEEs. METHOD: a novel microscale computational model of an epileptic neocortical column was introduced. This model incorporates the intricate multilayered structure of the cortex and allows for the simulation of realistic interictal epileptic signals. The proposed model was validated through comparisons with real IEEs recorded using intracranial stereo-electroencephalography (SEEG) signals from both humans and animals. Using the model, the user can recreate epileptiform patterns observed in different species (human, rodent, and mouse) and study the intracellular activity associated with these patterns. RESULTS: Our model allowed us to unravel the relationship between glutamatergic and GABAergic synaptic transmission of the epileptic neural network and the type of generated IEE. Moreover, sensitivity analyses allowed for the exploration of the pathophysiological parameters responsible for the transitions between these events. Finally, the presented modeling framework also provides an Electrode Tissue Model (ETI) that adds realism to the simulated signals and offers the possibility of studying their sensitivity to the electrode characteristics. CONCLUSION: The model (NeoCoMM) presented in this work can be of great use in different applications since it offers an in silico framework for sensitivity analysis and hypothesis testing. It can also be used as a starting point for more complex studies.

Pathways to epilepsy surgery in children with tuberous sclerosis complex-associated epilepsy.

BACKGROUND: Previous studies showed the efficacy of epilepsy surgery in carefully selected children with epilepsy associated with tuberous sclerosis complex. However, how this selection is conducted, and the characteristics of the patients brought to surgery are still poorly described. By conducting a multicentric retrospective cohort study covering the practice of the last twenty years, we describe the paths leading to epilepsy surgery in children with epilepsy associated with tuberous sclerosis complex. METHODS: We identified 84 children diagnosed with tuberous sclerosis complex and epilepsy by matching two exhaustive registries of genetic diseases and subsequent medical records reviews within two French neuropediatric and epilepsy centers. Demographic, clinical, longitudinal, and diagnostic and surgical procedures data were collected. RESULTS: Forty-six percent of the children were initially drug-resistant and 19% underwent resective surgery, most often before the age of four. Stereotactic electroencephalography was performed prior to surgery in 44% of cases. Fifty-seven and 43% of patients remained seizure-free one and ten years after surgery, respectively. In addition, 52% of initially drug-resistant patients who did not undergo surgery were seizure-free at the last follow-up. The number of anti-seizure medications required decreased in 50% of cases after surgery. Infantile spasms, intellectual disability, autism spectrum disorder or severe behavioral disorders were not contraindications to surgery but were associated with a higher rate of complications and a lower rate of seizure freedom after surgery. CONCLUSION: Despite the assumption of complex multifocal epilepsy and practical difficulties in young children with tuberous sclerosis complex, successful surgery results are comparable with other populations of patients with drug-resistant epilepsy, and a spontaneous evolution to drug-sensitive epilepsy may occur in non-operated patients.

Long-term Effect of Multichannel tDCS Protocol in Patients with Central Cortex Epilepsies Associated with Epilepsia Partialis Continua.

Epilepsia partialis continua (EPC) is a rare type of focal motor status epilepticus that causes continuous muscle jerking in a specific part of the body. Experiencing this type of seizure, along with other seizure types, such as focal motor seizures and focal to bilateral tonic-clonic seizures, can result in a disabling situation. Non-invasive brain stimulation methods like transcranial direct current stimulation (tDCS) show promise in reducing seizure frequency (SF) when medications are ineffective. However, research on tDCS for EPC and related seizures is limited. We evaluated personalized multichannel tDCS in drug-resistant EPC of diverse etiologies for long-term clinical efficacy We report three EPC patients undergoing a long-term protocol of multichannel tDCS. The patients received several cycles (11, 9, and 3) of five consecutive days of stimulation at 2 mA for 2 × 20 min, targeting the epileptogenic zone (EZ), including the central motor cortex with cathodal electrodes. The primary measurement was SF changes. In three cases, EPC was due to Rasmussen's Encephalitis (case 1), focal cortical dysplasia (case 2), or remained unknown (case 3). tDCS cycles were administered over 6 to 22 months. The outcomes comprised a reduction of at least 75% in seizure frequency for two patients, and in one case, a complete cessation of severe motor seizures. However, tDCS had no substantial impact on the continuous myoclonus characterizing EPC. No serious side effects were reported. Long-term application of tDCS cycles is well tolerated and can lead to a considerable reduction in disabling seizures in patients with various forms of epilepsy with EPC.

Basal temporal lobe epilepsy: SEEG electroclinical characteristics.

OBJECTIVE: Temporal lobe epilepsy is the most common type of focal drug-resistant epilepsy. Seizures with predominant involvement of basal temporal regions (BTR) are not well characterized. In this stereo electroencephalography (SEEG) study, we aimed at describing the ictal networks involving BTR and the associated clinical features. METHODS: We studied 24 patients explored with SEEG in our center with BTR sampling. We analyzed their seizures using a quantitative method: the "epileptogenicity index". Then we reported the features of the patients with maximal epileptogenicity within BTR, especially ictal network involved, ictal semiology and post-surgical outcome. RESULTS: We found that rhinal cortex, parahippocampal cortex and posterior fusiform gyrus were the most epileptogenic structures within the BTR (mean EI: 0.57, 0.55, 0.54 respectively). Three main groups of epileptogenic zone organization were found: anterior (23% of total seizures) posterior (30%) and global (47%, both anterior and posterior). Contralateral spread was found in 35% of left seizures and 20% of right seizures. Naming deficit was more prevalent in left BTR (71% vs 29% in right seizures; p = 0.01) whereas automatic speech production was preferentially represented in right seizures (11% vs 54%; p = 0.001). Surgery was proposed for 11 patients (45.8%), leading to seizure freedom in 72% (Engel Class I). One patient presented post-operative permanent functional deficit. CONCLUSION: Basal-temporal lobe epilepsy seems to be a specific entity among the temporal epilepsy spectrum with specific clinical characteristics. Resective surgery can be proposed with good outcomes in a significant proportion of patients and is safe provided that adequate language assessment has been preoperatively made.

Medical treatment of Rasmussen's Encephalitis: A systematic review.

Rasmussen's encephalitis (RE) is a severe, rare, chronic inflammatory brain disease resulting in drug-resistant epilepsy and progressive destruction of one hemisphere with loss of neurological function. RE is associated with a deterioration of background electroencephalography (EEG) activity, a progressive atrophy on magnetic resonance imaging (MRI) imaging and an extensive positron emission tomography hypometabolism over the affected hemisphere. RE is an immune-mediated disease, with a predominant role of CD8+ T cytotoxic cells, microglial cells, and activation of inflammasome pathway. The diagnosis of RE is based on clinical (intractable epilepsy and neurological deterioration), electrophysiological (unilateral EEG slowing) and MRI (hemiatrophy) criteria. Antiseizure medications are generally unable to stop seizures. The most effective procedure is hemispherotomy (surgical disconnection of one cerebral hemisphere), but this is associated with permanent motor and neurological deficits. Treatments targeting the immune system are recommended especially in the early stages of the disease or in patients with slow disease progression and mild deficits and/or not eligible for surgery. Based on the pathophysiology, several immunotherapies have been tried in RE (none exhaustively: corticosteroid, intravenous immunoglobulins, tacrolimus, azathioprine, adalimumab, mycophenolate mofetil, natalizumab). However, only small cohorts have been reported without comparative study. In this review, we will summarise some pathophysiological mechanisms of RE, before reporting the literature data concerning immunotherapies. We then discuss the limitations of these studies and the prospects for further research.

Predictive factors of postoperative outcome in the elderly after resective epilepsy surgery.

OBJECTIVE: To evaluate the efficiency of resective epilepsy surgery (RES) in patients over 50 years and determine prognostic factors. RESULTS: Over the 147 patients over 50 years (54.9±3.8 years [50-69]) coming from 8 specialized French centres for epilepsy surgery, 72.1%, patients were seizure-free and 91.2% had a good outcome 12 months after RES. Seizure freedom was not associated with the age at surgery or duration of epilepsy. In multivariate analysis, seizure freedom was associated with MRI and neuropathological hippocampal sclerosis (HS) (P=0.009 and P=0.028 respectively), PET hypometabolism (P=0.013), temporal epilepsy (P=0.01). On the contrary, the need for intracranial exploration was associated with a poorer prognosis (P=0.001). Postoperative number of antiepileptic drugs was significantly lower in the seizure-free group (P=0.001). Neurological adverse event rate after surgery was 21.1% and 11.7% of patients had neuropsychological adverse effects overall transient. CONCLUSIONS: RES is effective procedure in the elderly. Even safe it remains at higher risk of complication and population should be carefully selected. Nevertheless, age should not be considered as a limiting factor, especially when good prognostic factors are identified.

The Bayesian Virtual Epileptic Patient: A probabilistic framework designed to infer the spatial map of epileptogenicity in a personalized large-scale brain model of epilepsy spread.

Despite the importance and frequent use of Bayesian frameworks in brain network modeling for parameter inference and model prediction, the advanced sampling algorithms implemented in probabilistic programming languages to overcome the inference difficulties have received relatively little attention in this context. In this technical note, we propose a probabilistic framework, namely the Bayesian Virtual Epileptic Patient (BVEP), which relies on the fusion of structural data of individuals to infer the spatial map of epileptogenicity in a personalized large-scale brain model of epilepsy spread. To invert the individualized whole-brain model employed in this study, we use the recently developed algorithms known as No-U-Turn Sampler (NUTS) as well as Automatic Differentiation Variational Inference (ADVI). Our results indicate that NUTS and ADVI accurately estimate the degree of epileptogenicity of brain regions, therefore, the hypothetical brain areas responsible for the seizure initiation and propagation, while the convergence diagnostics and posterior behavior analysis validate the reliability of the estimations. Moreover, we illustrate the efficiency of the transformed non-centered parameters in comparison to centered form of parameterization. The Bayesian framework used in this work proposes an appropriate patient-specific strategy for estimating the epileptogenicity of the brain regions to improve outcome after epilepsy surgery.

Malformations of cortical development: The role of 7-Tesla magnetic resonance imaging in diagnosis.

Comparison studies between 7T and 1.5 or 3T magnetic resonance imaging (MRI) have demonstrated the added value of ultra-high field (UHF) MRI to better identify, delineate and characterize malformations of cortical development (MCD), and to disambiguate doubtful findings observed at lower field strengths. High resolution structural sequences such as magnetization prepared two rapid acquisition gradient echoes (MP2RAGE), fluid and white matter suppression MP2RAGE (FLAWS), and susceptibility-weighted imaging (SWI) appear to be key to the improvement of MCD diagnosis in clinical practice. 7T MRI offers not only images of high resolution and contrast but also provides many quantitative approaches capable of acting as more efficient probes of microstructure and ameliorating the categorization of MCDs. Post-processing of multiparametric ultra-high resolution and quantitative data may also be used to improve automated detection of MCD via machine learning. Therefore, 7T MRI can be considered as a useful tool in the presurgical evaluation of drug-resistant partial epilepsies, particularly, but not exclusively, in cases of normal appearing conventional MRI. It also opens many perspectives in the fields of in vivo histology and computational anatomy.

Time rescaling reproduces EEG behavior during transition from propofol anesthesia-induced unconsciousness to consciousness.

General anesthesia (GA) is a reversible manipulation of consciousness whose mechanism is mysterious at the level of neural networks leaving space for several competing hypotheses. We recorded electrocorticography (ECoG) signals in patients who underwent intracranial monitoring during awake surgery for the treatment of cerebral tumors in functional areas of the brain. Therefore, we recorded the transition from unconsciousness to consciousness directly on the brain surface. Using frequency resolved interferometry; we studied the intermediate ECoG frequencies (4-40 Hz). In the theoretical study, we used a computational Jansen and Rit neuron model to simulate recovery of consciousness (ROC). During ROC, we found that f increased by a factor equal to 1.62 ± 0.09, and δf varied by the same factor (1.61 ± 0.09) suggesting the existence of a scaling factor. We accelerated the time course of an unconscious EEG trace by an approximate factor 1.6 and we showed that the resulting EEG trace match the conscious state. Using the theoretical model, we successfully reproduced this behavior. We show that the recovery of consciousness corresponds to a transition in the frequency (f, δf) space, which is exactly reproduced by a simple time rescaling. These findings may perhaps be applied to other altered consciousness states.

Brain molecular imaging in pharmacoresistant focal epilepsy: Current practice and perspectives.

This review aims to synthesize all the available data on brain molecular imaging, such as single-photon emission computed tomography (SPECT) and interictal fluorodeoxyglucose positron emission tomography (FDG-PET), in focal epilepsies. SPECT imaging is able to measure regional cerebral blood flow and its major innovation remains its ictal imaging value. On the other hand, FDG-PET, which has higher spatial resolution and lower background activity than SPECT, enables glycolytic metabolism to be identified in interictal states. Therefore, interictal FDG-PET has greater sensitivity than interictal SPECT, especially in temporal lobe epilepsies (TLEs). Thus, 18F-FDG-PET is a necessary step in the presurgical evaluation of TLEs, but also of extratemporal epilepsies (ETEs), contributing to >30% of the decision to undertake surgery. In addition, FDG-PET has particular diagnostic value in focal epilepsies showing normal magnetic resonance imaging (MRI). PET also has good prognostic value for post-surgical outcomes as well as cognitive impairment, especially in cases where the hypometabolism extent is limited. Moreover, the notion of an epileptic network is well highlighted by functional PET imaging, allowing better understanding of the pathological substrates of these disorders. Future development of quantitative analysis software and of novel radiotracers and cameras will certainly enhance its clinical usefulness.

PDGFRß(+) cells in human and experimental neuro-vascular dysplasia and seizures.

INTRODUCTION: Neuro-vascular rearrangement occurs in brain disorders, including epilepsy. Platelet-derived growth factor receptor beta (PDGFRß) is used as a marker of perivascular pericytes. Whether PDGFRß(+) cell reorganization occurs in regions of neuro-vascular dysplasia associated with seizures is unknown. METHODS: We used brain specimens derived from epileptic subjects affected by intractable seizures associated with focal cortical dysplasia (FCD) or temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). Tissues from cryptogenic epilepsy, non-sclerotic hippocampi or peritumoral were used for comparison. An in vivo rat model of neuro-vascular dysplasia was obtained by pre-natal exposure to methyl-axozy methanoic acid (MAM). Status epilepticus (SE) was induced in adult MAM rats by intraperitoneal pilocarpine. MAM tissues were also used to establish organotypic hippocampal cultures (OHC) to further assess pericytes positioning at the dysplastic microvasculature. PDGFRß and its colocalization with RECA-1 or CD34 were used to segregate perivascular pericytes. PDGFRß and NG2 or IBA1 colocalization were performed. Rat cortices and hippocampi were used for PDGFRß western blot analysis. RESULTS: Human FCD displayed the highest perivascular PDGFRß immunoreactivity, indicating pericytes, and presence of ramified PDGFRß(+) cells in the parenchyma and proximal to microvessels. Tissues deriving from human cryptogenic epilepsy displayed a similar pattern of immunoreactivity, although to a lesser extent compared to FCD. In TLE-HS, CD34 vascular proliferation was paralleled by increased perivascular PDGFRß(+) pericytes, as compared to non-HS. Parenchymal PDGFRß immunoreactivity co-localized with NG2 but was distinct from IBA1(+) microglia. In MAM rats, we found pericyte-vascular changes in regions characterized by neuronal heterotopias. PDGFRß immunoreactivity was differentially distributed in the heterotopic and adjacent normal CA1 region. The use of MAM OHC revealed microvascular-pericyte dysplasia at the capillary tree lining the dentate gyrus (DG) molecular layer as compared to control OHC. Severe SE induced PDGFRß(+) immunoreactivity mostly in the CA1 region of MAM rats. CONCLUSION: Our descriptive study points to microvascular-pericyte changes in the epileptic pathology. The possible link between PDGFRß(+) cells, neuro-vascular dysplasia and remodeling during seizures is discussed.

[Epilepsy surgery in France]. / La chirurgie de l'épilepsie en France Evaluation de l'activité

We report here the results of the first survey on epilepsy surgery activity in France. Data from a questionnaire sent to 17 centers practicing epilepsy surgery were analyzed. All centers responded; however, all items were not completely documented. Over 50 years, more than 5000 patients have been operated on for drug-resistant epilepsy and more than 3000 patients underwent some invasive monitoring, most often SEEG. Currently, nearly 400 patients (including more than 100 children) are operated on yearly for epilepsy in France. Over a study period varying among centers (from two to 20 years; mean, 9.5 years), results from more than 2000 patients including one-third children were analyzed. Important differences between adults and children, respectively, were observed in terms of location (temporal: 72% versus 4.3%; frontal: 12% versus 28%; central: 2% versus 11%), etiology (hippocampal sclerosis: 41% versus 2%; tumors 20% versus 61%); and procedures (cortectomy: 50% versus 23%; lesionectomy: 8% versus 59%), although overall results were identical (seizure-free rates following temporal lobe surgery: 80.6% versus 79%; following extratemporal surgery: 65.9% versus 65%). In adults, the best results were observed following temporomesial (TM) resection associated with hippocampal sclerosis or other lesions (class I: 83% and 79%, respectively), temporal neocortical (TNC) lesional (82%), while resections for cryptogenic temporal resections were followed by 69% (TM) and 63% (TNC) class I outcome. Extratemporal lesional resections were associated with 71% class I outcome and cryptogenic 43%. In children, the best results were obtained in tumor-associated epilepsy regardless of location (class I: 80%). A surgical complication occurred in 8% after resective surgery - with only 2.5% permanent morbidity - and 4.3% after invasive monitoring (mostly hemorrhagic). Overall results obtained by epilepsy surgery centers were in the higher range of those reported in the literature, along with a low rate of major surgical complications. Growing interest for epilepsy surgery is clearly demonstrated in this survey and supports further development to better satisfy the population's needs, particularly children. Activity should be further evaluated, while existing epilepsy surgery centers as well as healthcare networks should be expanded.

Long-term efficacy of gamma knife radiosurgery in mesial temporal lobe epilepsy.

BACKGROUND: Gamma knife (GK) radiosurgery has been proposed as an alternative to classic microsurgery in mesial temporal lobe epilepsy (MTLE). Short-term follow-up studies have reported encouraging results, but long-term efficacy is not known. OBJECTIVE: To report the efficacy and tolerance of GK radiosurgery in MTLE after a follow-up > 5 years. METHODS: Patients with a follow-up > 5 years presenting with MTLE and treated with a marginal dose of 24 Gy were included in the study. RESULTS: Fifteen patients were included. Eight were treated on the left side, and 7 were treated on the right. The mean follow-up was 8 years (range 6-10 years). At the last follow-up, 9 of 16 patients (60%) were considered seizure free (Engel Class I) (4/16 in Class IA, 5/16 in Class IB). Seizure cessation occurred with a mean delay of 12 months (+/- 3) after GK radiosurgery, often preceded by a period of increasing aura or seizure occurrence (6/15 patients). The mean delay of appearance of the first neuroradiologic changes was 12 months (+/- 4). Nine patients (60%) experienced mild headache and were placed on corticosteroid treatment for a short period. All patients who were initially seizure free experienced a relapse of isolated aura (10/15, 66%) or complex partial seizures (10/15, 66%) during antiepileptic drug tapering. Restoration of treatment resulted in good control of seizures. CONCLUSION: Gamma knife radiosurgery is an effective and safe treatment for mesial temporal lobe epilepsy. Results are maintained over time with no additional side effects. Long-term results compare well with those of conventional surgery.

[Radiosurgery for drug-resistant epilepsies: state of the art, results and perspectives]. / Rôle de la radiochirugie Gamma Knife dans le traitement des épilepsies pharmacorésistantes: situation actuelle, résultats et perspectives.

BACKGROUND: There is growing interest in the use of radiosurgery in epilepsy. We analyzed our experience in this field in an attempt to define the potential of radiosurgery in epileptology. MATERIAL AND METHODS: [corrected] Our local clinical experience (134 patients), accumulated over the last 15 years, mainly includes treatment of temporal lobe epilepsy without space-occupying lesions (59 patients), including 53 with pure MTLE, 61 cases of hypothalamic hamartoma, two cases of callosotomy, and 12 other types of epilepsy. RESULTS: The analysis of our material, as well as other clinical and experimental data, suggest that the use of radiosurgery is beneficial only to patients in whom a strict preoperative definition of the extent of the epileptogenic zone (or network) has been achieved and strict rules of dose planning have been applied. As soon as these principles are not observed, the risk of treatment failure and/or side effects increases dramatically. Long-term outcome data are now available and published for MTLE but not yet for other types of epilepsy. Long-term safety and efficacy in MTLE are comparable to surgical resection but radiosurgery has the advantage of sparing verbal memory in patients operated by Gamma Knife (GK) on the dominant side. In small hamartomas, the efficacy is comparable to microsurgery but with a dramatic reduction in risk. CONCLUSION: The vast amount of clinical materiel and long-term evaluation now support the use of GK surgery in small hypothalamic hamartomas and MTLE when the patient is at risk of verbal memory loss.

The influence of low-grade glioma on resting state oscillatory brain activity: a magnetoencephalography study.

PURPOSE: In the present MEG-study, power spectral analysis of oscillatory brain activity was used to compare resting state brain activity in both low-grade glioma (LGG) patients and healthy controls. We hypothesized that LGG patients show local as well as diffuse slowing of resting state brain activity compared to healthy controls and that particularly global slowing correlates with neurocognitive dysfunction. PATIENT AND METHODS: Resting state MEG recordings were obtained from 17 LGG patients and 17 age-, sex-, and education-matched healthy controls. Relative spectral power was calculated in the delta, theta, upper and lower alpha, beta, and gamma frequency band. A battery of standardized neurocognitive tests measuring 6 neurocognitive domains was administered. RESULTS: LGG patients showed a slowing of the resting state brain activity when compared to healthy controls. Decrease in relative power was mainly found in the gamma frequency band in the bilateral frontocentral MEG regions, whereas an increase in relative power was found in the theta frequency band in the left parietal region. An increase of the relative power in the theta and lower alpha band correlated with impaired executive functioning, information processing, and working memory. CONCLUSION: LGG patients are characterized by global slowing of their resting state brain activity and this slowing phenomenon correlates with the observed neurocognitive deficits.

Gamma knife surgery for epilepsy related to hypothalamic hamartomas.

OBJECTIVE: Drug resistant epilepsy associated with hypothalamic hamartoma (HH) can be cured by microsurgical resection of the lesion. Morbidity and mortality risks of microsurgery in this area are significant. Gamma Knife Surgery's (GKS) reduced invasivity seems to be well adapted. In view of the severity of the disease and risks of surgical resection it is crucial to evaluate GKS for this indication. A first retrospective study has shown a very good safety and efficacy level but for a more reliable evaluation a prospective study would be required. METHODS: Between Oct 1999 and July 2002, 30 patients with HH and associated severe epilepsy were included. Seizure semiology (video EEG) and frequency, behavioural disturbances, neuropsychological performance, endocrinological status, sleep electroclinical abnormalities, MR imaging, and visual function were systematically evaluated before and after GKS (6, 12, 18, 24, 36 months). Twenty patients had experienced precocious puberty at a median age of 3,7 (0-9). Range of maximum diameter was from 7,5 to 23 mm with only 3 larger than 18 mm. The median marginal dose was 17 gy (14-20). RESULTS: Sufficient follow up for final evaluation is not yet available. Only 6 patients have a follow-up of more than 12 months and 19 more than 6 months. However a lot of very dramatic changes did occur during that period in this group. Among the 19 patients with more than 6 months of follow-up, a lot had already experienced an increase of gelastic seizures around 3 months (3), an improvement in their seizure rate (18), behaviour (9), sleep (3), and EEG background activity (3), a cessation of partial complex seizures (7). No complications have occurred till now except one patient experiencing at 5 months a hyperthermia without infection and concomitant increase of gelastic seizures both ceasing suddenly and spontaneously after 15 days. CONCLUSION: Our first results indicate that GKS is as effective as microsurgical resection and very much safer. GKS also allows to avoid the vascular risk related to radiofrequency lesioning or stimulation. The disadvantage of radiosurgery is its delayed action. Longer follow-up is mandatory for a serious evaluation of the role of GKS. Results are faster and more complete in patients with smaller lesions inside the 3rd ventricle (grade II). The early effect on subclinical discharges turns out to play a major role in the dramatic improvement of sleep quality, behaviour, developmental acceleration at school.

What role for radiosurgery in mesial temporal lobe epilepsy.

SUMMARY: The Gamma Knife radiosurgery is a neurosurgical approach having now demonstrated well its efficiency, its low morbidity and its comfort in the treatment of numerous neurosurgical disorders. These advantages of this type of intervention make it a method of great interest in functional neurosurgery and quite particularly in surgery of epilepsy. French experience is a pioneer one in this domain. Since for several years the positive evolution of the epilepsy associated with brain lesions had been noticed after radiosurgical Gamma Knife treatment, the use of this approach in surgery of epilepsy has been systematically evaluated since 1993. Data are today available concerning the surgical treatment of the epilepsies originating in the temporomesial area without space-occupying process, epilepsies associated to hypothalamic hamartomas and epilepsies associated with cavernous angiomas or low grade gliomas. The quality of the epileptological result obtained in these various indications associated with a very reduced morbidity lets assume that the Gamma Knife radiosurgery could indeed have tomorrow a place within the sample group of surgical approaches dedicated to the treatment of severe epilepsies. However, a larger number of treated patients and a more prolonged follow-up remains necessary to assess this approach in a more definitive way.

Gamma Knife surgery, a neuromodulation therapy in epilepsy surgery!

INTRODUCTION: The more classical approach for Epilepsy surgery is the removal of the epileptogenic zone (ZE). We present a critical review of information in favor of a possible non-destructive effect of radiosurgery in epilepsy surgery. MATERIAL: Clinical material of patients with epilepsies related to a lesion in highly functional areas subjected to radiosurgery with relief of the seizures and no functional worsening is available. We applied direct treatment of the EZ with good efficacy in the absence of destructive aspects on the MR and no functional deterioration (e.g. hypothalamic hamartomas). Experimental studies have shown biochemical differential effect of radiosurgery on the striatum, glial cell elimination, stem cell migration toward the target area, sprouting,... Plasticity phenomenon are induced by radiosurgery when using non necrotizing dosemetry. DISCUSSION: There is clinical and experimental evidence of Gamma Knife capability to induce modulation in the neural system. Detailed mechanism of this modulation and dosemetric parameters enabling to induce such plasticity with no necrosis are still unknown. Subpial transection turning out actually to be quite disappointing, there is a specific rationale to test radiosurgery capability to treat EZ cortex while preserving the underlying function of this cortex when the functional risk for cortectomy is too high.

[Gamma knife radiosurgery for the treatment of severe epilepsy]. / Rôle de la radiochirurgie Gamma Knife dans le traitement des épilepsies sévères.

The Gamma Knife radiosurgery is a neurosurgical approach having now demonstrated well its efficiency, its low morbidity and its comfort in the treatment of numerous neurosurgical disorders. These advantages of this type of intervention make it a method of great interest in functional neurosurgery and quite particularly in surgery of epilepsy. French experience is a pionner one in this domain. If for several years the positive evolution of the epilepsy associated to brain lesions had been noticed after the Gamma Knife radiosurgical treatment, the use of this approach in surgery of the epilepsy is systematically estimated since 1993. Data are today available concerning the surgical treatment of the epilepsies originating in temporomesiale area without occupying process, epilepsies associated to hypothalamic hamartomas and epilepsies associated to cavernous angiomas or to low grade gliomas. The quality of the epileptological result obtained in these various indications associated to a very reduced morbidity lets suppose that the Gamma Knife radiosurgery could indeed have tomorrow a place within the sample group of surgical approaches dedicated to the treatment of severe epilepsies. However, a larger number of treated patients and a more prolonged follow-up remains necessary to estimate in a more definitive way this approach.

[The presurgical evaluation of epilepsies]. / Les investigations préchirurgicales des épilepsies.

In this article, we present an overview of the principles, practices and procedures of the presurgical evaluation of the epilepsies in use in our center and in the majority of French teams. Surgery for epilepsy is offered to patients presenting with severe epilepsy with partial seizures. Its aim is to stop the seizures, or to significantly reduce their frequency. To do that, the epileptogenic zone should theoretically be removed and/or the propagation pathways of the seizures should be cut. Discussion of these indications inevitably includes prior assessment of the functional sequels (sensory, motor, cognitive or behavioral) which surgery is liable cause. The presurgical evaluation involves a multidisciplinary approach involving epileptologists, neurophysiologists, neuroradiologists, neuropsychologists and neurosurgeons and is carried out in two phases. The phase I is based on non-invasive investigations, including functional and structural neuroimaging, neuropsychological assessment, source localization of interictal spike and video-EEG recordings of seizures. The phase II is often required and is aimed to precisely define the anatomical localization of the epileptogenic zone and the relationships with a structural lesion. This invasive phase is mainly based on stereoelectroencephalography (SEEG). Finally, the surgical procedure must be adapted according to the distribution and dynamics of the anatomical and functional abnormalities which individually define each case of epilepsy.