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Purpose: To evaluate the efficacy, dose–response, tolerability, and withdrawal effects of levetiracetam (Keppra®) as adjunctive therapy in adult patients with partial epilepsy. Methods: In this European multicenter, double-blind, randomized, cross-over trial, levetiracetam 1000 or 2000 mg/day given in two divided doses was compared to placebo as add-on therapy in 324 patients with refractory partial seizures with or without secondary generalization. This trial consisted of six periods: an 8- or 12-week baseline, a treatment period A (4-week titration and 12-week evaluation), a treatment period B (4-week titration and 12-week evaluation), and a withdrawal period. During each evaluation period (A and B), patients received two of the three possible treatment regimens. Results: This study provides additional information on dose–response effects and withdrawal phenomena and confirms the responder and seizure freedom rates previously reported in the parallel part of the study (Epilepsia 41 (2000) 1179–1186). Both doses of levetiracetam significantly decreased mean partial seizure frequency compared with placebo (P<0.001), and significantly more patients receiving levetiracetam had ≥50 and ≥75% reductions in partial seizure frequency (1000 mg, P=0.004 and P=0.043, respectively; 2000 mg P=0.001 and P<0.001, respectively). In addition, 5.5% (10/183) of patients receiving levetiracetam 1000 mg/day and 6.3% (11/175) of patients receiving levetiracetam 2000 mg/day were seizure-free during the corresponding evaluation period, compared with 1.2% (2/172) of patients on placebo. A within-patient comparison revealed a significantly greater responder rate for the higher levetiracetam dose (P=0.018). The most commonly reported adverse effects (≥5% and more frequent in one of the groups with levetiracetam) were headache, asthenia, infection, somnolence, pharyngitis, dizziness, and pain. No withdrawal-related adverse events were reported during the cross-titration period. Conclusions: Levetiracetam was effective and well-tolerated and decreased seizure frequency in a dose-dependent manner, with no evidence of typical withdrawal-related adverse events or rebound phenomena after withdrawal or down-titration. [Copyright &y& Elsevier]

Left and right prefrontal, premotor, and anterior temporal sites were stereotaxically implanted in order to direct surgical therapy for epilepsy. Direct electrical stimulation of the right anterior inferior frontal gyrus resulted in face-related hallucinations and illusions. When the patient was viewing a blank background, stimulation induced the experience of a rapid succession of faces. When the patient was viewing a real face, stimulation induced a series of modifications to that face. Effective stimulations induced afterdischarges that remained localised to right ventrolateral prefrontal cortex (VLPFC). Stimulation of other frontal and anterior temporal sites, bilaterally, induced no face-related hallucinations or illusions. This result supports a contribution of right VLPFC to face processing, and is consistent with models wherein it activates representations in working or declarative memories. [ABSTRACT FROM AUTHOR]

Objective: To study whether sensory afferents of the hand projected directly to the primary motor cortex (M1) as they have been well electrophysiologically described in monkeys but not in humans.Methods: We recorded intracerebrally in the central areas (pre- and/or postcentral gyrus) somatosensory evoked potentials (SEPs) to median nerve stimulation in 5 (4 women, 1 man; age 14–37 years) epileptic patients during presurgical evaluation.Results: The primary somatosensory cortex (S1) showed negative–positive components peaking at about 20 and 30 ms, respectively. By contrast, M1 disclosed SEPs of two types of waveforms depending on the portion of the precentral gyrus explored by the different contacts of the electrode. Here, we demonstrated, for the first time, in the medial portion of M1, shaped like an omega in the axial plane, corresponding to the motor hand area, the occurrence of a primary negative component as in S1, but of higher amplitude and peaking at about 4 ms later. In other respects, the lateral portion of M1 disclosed positive–negative components peaking at about 21 and 31 ms, respectively.Conclusions: These electrophysiological findings, based on accurate spatial and temporal resolution of intracerebral recordings, suggested that somatosensory inputs from the hand projected directly to M1 in its medial portion. [Copyright &y& Elsevier]

Studies the suitable treatment for malignant tumors of the salivary glands. Prognostic factors for the disease; Application of surgery in combination with radiotherapy for the treatment of the disease.

Purpose: To determine the relative biological effectiveness (RBE) for initial and delayed inactivation of cells by a modulated proton beam suitable for the treatment of tumours of the eye, within the spread-out Bragg peak and in its distal declining edge. Materials and methods: Human tumour SCC25 cells were irradiated with the 65 MeV proton beam at the Cyclotron Medicyc in Nice. Perspex plates of different thickness were used to simulate five positions along the beam line: 2 mm corresponding to the entrance beam; 15.6 and 25mm in the spread-out Bragg peak; 27.2 and 27.8mm for the distal edge. At each position clonogenic survival of the irradiated cells and of their progeny were determined at various dose values. [sup 60]Co γ-rays were used as reference radiation. Results: RBE values evaluated at the survival level given by 2 Gy of γ-rays increased with increasing depth from close to 1.0 at the proximal to about 1.2 at the distal part of the peak. Within the declining edge it reached the value of about 1.4 at 27.2 and about 2 at 27.8 mm. For the progeny of irradiated cells, the RBE value ranged from 1.0 to 1.1 within the spread-out Bragg peak and then increased up to a value of 2.0 at the last position. The dose-effect curves for the progeny always had a larger shoulder than for the irradiated progenitors, their α parameters being lower by a factor of about 4 and their β parameters always being higher. The alpha/beta ratio was about 50Gy for the progenitors and about 6Gy for their progeny. The incidence of delayed eÚects increased with dose and with the depth within the beam. Conclusions: RBE values for the inactivation of cells irradiated in the spread-out Bragg peak are compatible with the value currently assumed in clinical applications. In the distal declining edge of the beam, the RBE values increased significantly to an extent that may be of concern when the region of the treatment volume is close to sensitive tissues. The yield of delayed reproductive cell death was significant at each position along the beam line. [ABSTRACT FROM AUTHOR]

The patient described in the companion paper by Vignal, Chauvel, and Halgren (this issue) was studied with event related potentials (ERPs) recorded directly within the brain substance, as well as with neuropsychological tests before and after therapeutic cortectomy. Large ERPs were evoked in the prefrontal cortex to faces, as compared to sensory controls and words. The largest such ERPs were highly localised to the same right anterior inferior prefrontal site where direct electrical stimulation resulted in face hallucinations. Face-selective ERPs were also evoked in the right prefrontal sites that had shown projected activity during face hallucinations, and near the right anterior superior temporal sulcus. Selective responses began about 150msec after face onset. Words, but not faces or sensory controls, evoked large ERPs in distinct locations, mainly in the left hemisphere. A successful surgical therapy was performed by removing the cortex surrounding the right prefrontal site where face-selective responses were recorded and where face hallucinations were evoked by stimulation. This cortectomy resulted in a severe deficit in the recognition of emotional facial expressions, especially fear. No change was noted, however, in the recall of emotional words, or other tasks. The current results provide strong support for the early, specific, and sustained involvement of a multi-focal network in the right inferior fronto-temporal cortex in face-processing. [ABSTRACT FROM AUTHOR]

Individual variability has clear effects upon the outcome of therapies and treatment approaches. The customization of healthcare options to the individual patient should accordingly improve treatment results. We propose a novel approach to brain interventions based on personalized brain network models derived from non-invasive structural data of individual patients. Along the example of a patient with bitemporal epilepsy, we show step by step how to develop a Virtual Epileptic Patient (VEP) brain model and integrate patient-specific information such as brain connectivity, epileptogenic zone and MRI lesions. Using high-performance computing, we systematically carry out parameter space explorations, fit and validate the brain model against the patient's empirical stereotactic EEG (SEEG) data and demonstrate how to develop novel personalized strategies towards therapy and intervention. [ABSTRACT FROM AUTHOR]

Picture naming is a standard task used to probe language processes in healthy and impaired speakers. It recruits a broad neural network of language related areas, among which the hippocampus is rarely included. However, the hippocampus could play a role during picture naming, subtending, for example, implicit learning of the links between pictured objects and their names. To test this hypothesis, we recorded hippocampal activity during plain picture naming, without memorization requirement; we further assessed whether this activity was modulated by contextual factors such as repetition priming and semantic interference. Local field potentials recorded from intracerebral electrodes implanted in the healthy hippocampi of epileptic patients revealed a specific and reliable pattern of activity, markedly modulated by repetition priming and semantic context. These results indicate that the hippocampus is recruited during picture naming, presumably in relation to implicit learning, with contextual factors promoting differential hippocampal processes, possibly subtended by different sub-circuitries. [ABSTRACT FROM AUTHOR]

Abstract: Rapid discharges (25–80Hz), a characteristic EEG pattern often recorded at seizure onset in partial epilepsies, are often considered as electrophysiological signatures of the epileptogenic zone. While the recording of rapid discharges from intracranial electrodes has long been established, their observation from the scalp is challenging. The prevailing view is that rapid discharges cannot be seen clearly (or at all) in scalp EEG because they have low signal-to-noise ratio. To date, however, no studies have investigated the ‘observability’ of rapid discharges, i.e. under what conditions and to what extent they can be visible in recorded EEG signals. Here, we used a model-based approach to examine the impact of several factors (distance to sources, skull conductivity, source area, source synchrony, and background activity) on the observability of rapid discharges in simultaneously simulated depth EEG and scalp EEG signals. In our simulations, the rapid discharge was clearly present in depth EEG signals but mostly almost not visible in scalp EEG signals. We identified some of the factors that may limit the observability of the rapid discharge on the scalp. Notably, surrounding background activity was found to be the most critical factor. The findings are discussed in relation to the presurgical evaluation of epilepsy. [Copyright &y& Elsevier]

Abstract: In addition to the hippocampus, the entorhinal/perirhinal cortices are often involved in temporal lobe epilepsy (TLE). It has been proposed that these anterior parahippocampal structures play a key role in recognition memory. We studied the voxel-based PET correlation between number of correctly recognized targets in a new recognition memory paradigm and interictal cerebral metabolic rate for glucose, in 15 patients with TLE with hippocampal sclerosis. In comparison to healthy subjects, patients had decreased recognition of targets (P <0.001) and ipsilateral hypometabolism (relative to side of hippocampal sclerosis) of the hippocampus, entorhinal/perirhinal cortices, medial temporal pole, and middle temporal gyrus (P <0.05, corrected by false discovery rate method). Performance correlated with interictal metabolism of ipsilateral entorhinal/perirhinal cortices (P <0.005, Spearman''s rank test), but this relationship was not significant in the hippocampus itself (P >0.18, Spearman''s rank test). These findings highlight the preferential involvement of entorhinal/perirhinal cortices in recognition memory in patients with TLE, and suggest that recognition memory paradigms may be useful in assessing anterior parahippocampal functional status in TLE. [Copyright &y& Elsevier]

Abstract: Background: Simultaneous EEG-fMRI can reveal haemodynamic changes associated with epileptic activity which may contribute to understanding seizure onset and propagation. Methods: Nine of 83 patients with focal epilepsy undergoing pre-surgical evaluation had seizures during EEG-fMRI and analysed using three approaches, two based on the general linear model (GLM) and one using independent component analysis (ICA): [1.] EEGs were divided into up to three phases: early ictal EEG change, clinical seizure onset and late ictal EEG change and convolved with a canonical haemodynamic response function (HRF) (canonical GLM analysis). [2.] Seizures lasting three scans or longer were additionally modelled using a Fourier basis set across the entire event (Fourier GLM analysis). [3.] Independent component analysis (ICA) was applied to the fMRI data to identify ictal BOLD patterns without EEG. The results were compared with intracranial EEG. Results: The canonical GLM analysis revealed significant BOLD signal changes associated with seizures on EEG in 7/9 patients, concordant with the seizure onset zone in 4/7. The Fourier GLM analysis revealed changes in BOLD signal corresponding with the results of the canonical analysis in two patients. ICA revealed components spatially concordant with the seizure onset zone in all patients (8/9 confirmed by intracranial EEG). Conclusion: Ictal EEG-fMRI visualises plausible seizure related haemodynamic changes. The GLM approach to analysing EEG-fMRI data reveals localised BOLD changes concordant with the ictal onset zone when scalp EEG reflects seizure onset. ICA provides additional information when scalp EEG does not accurately reflect seizures and may give insight into ictal haemodynamics. [ABSTRACT FROM AUTHOR]

Background: Reading epilepsy is a rare form of epilepsy, classified among idiopathic, age- and localisation-related (partial) epilepsies as a reflex epilepsy syndrome. Seizures usually consist of myoclonic jerks restricted to the jaw. However, distinct ictal features including visual symptoms and paroxysmal a- or dyslexia are described in some patients. The anatomical substrate of ictogenesis in reading epilepsy remains poorly understood.Methods: The authors report here the case of a primary reading epilepsy for which ictal semiology was characterised by visual symptoms and dyslexia, investigated by MRI, interictal high-resolution EEG and PET, ictal video-EEG and SPECT. Brain MRI was normal. Interictal high-resolution EEG was performed with 64 scalp channels, a realistic head model and different algorithms to solve the inverse problem.Results: Interictal source localisations highlighted the left occipito-temporal junction. Interictal PET demonstrated bilateral occipito-temporal hypometabolism with left-sided predominance. Ictal EEG showed a rhythmic discharge in left temporo-parieto-occipital junction channels, with left occipito-temporal predominance. MRI fusion of the coregistered subtraction between ictal and interictal SPECT individualised relative hyperperfusion affecting (a) the left occipito-parietal junction area, (b) the left lateral middle and inferior temporal gyri and (c) the left inferior frontal area.Conclusion: Besides reading-induced myoclonic jerks of the jaw, a second variant of reading epilepsy exists with clearly partial seizures manifested by visual symptoms and a- or dyslexia. These seizures originate from the occipito-temporal region of the dominant hemisphere, corresponding to the posterior part of the neural network that underlies the function of reading. [ABSTRACT FROM AUTHOR]

Summary: Purpose: Hyperkinetic seizures are most often considered to originate from prefrontal cortex. Recently however, it has been suggested that hyperkinetic seizures can be found in patients with temporal lobe seizures. The objective of this study was to determine the features of temporal epilepsy with hyperkinetic seizures and the functional anatomy of involved brain networks. Methods: We retrospectively identified patients investigated by depth electrodes (SEEG) in whom hyperkinetic manifestations were proved to be linked to initial temporal lobe involvement. Seizure organisation was determined according to the “Epileptogenicity Index” (EI), a new way to quantify rapid discharges at seizure onset. Results: We found 7 patients among 130 SEEG investigations that fulfilled the inclusion criteria. Most of the patients presented with hyperkinetic occurring (or predominating) during sleep. SEEG signal analysis demonstrated a common temporo-frontal network in which the temporal pole played a central role. Major involvement of the orbito-frontal cortex and to a lesser extent the cingulate gyrus was also a particular feature of these seizures. Discussion: Seizures originating in the temporal lobe must be recognized as an important cause of hyperkinetic seizures. The temporal pole and its connexions with medio-basal prefrontal cortex represent the main structures involved in epileptogenic networks. [Copyright &y& Elsevier]

Abstract: In many applications which make use of EEG to investigate brain functions, a central question is often to relate the recorded signals to the spatio-temporal organization of the underlying neuronal sources of activity. A modeling attempt to quantitatively investigate this imperfectly known relationship is reported. The proposed plausible model of EEG generation relies on an accurate representation of the neuronal sources of activity. It combines both an anatomically realistic description of the spatial features of the sources (convoluted dipole layer) and a physiologically relevant description of their temporal activities (coupled neuronal populations). The model was used in the particular context of epileptiform activity (interictal spikes) to interpret simultaneously generated scalp and intracerebral EEG. Its integrative properties allowed for the bridging between source-related parameters (spatial extent, location, synchronization) and the properties of resulting EEG signals (amplitude of spikes, amplitude gradient along intracerebral electrodes, topography over scalp electrodes). The sensitivity of both recording modalities to source-related parameters was also studied. The model confirmed that the cortical area involved in interictal spikes is rather large. Its relative location with respect to recording electrodes was found to strongly influence the properties of EEG signals as the source geometry is a critical parameter. The influence, on simulated signals, of the synchronization degree between neuronal populations within the epileptic source was also investigated. The model revealed that intracerebral EEG can reflect epileptic activities corresponding to weak synchronization between neuronal populations of the epileptic patch. These results, as well as the limitations of the model, are discussed. [Copyright &y& Elsevier]

Abstract: The aim of this study was to better understand the significance of interictal changes in water molecule diffusivity defined by diffusion-weighted imaging (DWI) in frontal lobe epilepsy (FLE), as well as to test the accuracy of interictal DWI in the definition of the epileptogenic zone (EZ). DWI was carried out in 14 patients with refractory FLE (9 negative-MRI) as well as in 25 controls. Statistical mapping analysis (SPM2) of diffusivity maps was used to detect, for each subject, significant diffusivity alterations. We then studied the relationships between diffusion and depth recorded electrical abnormalities. Clinical correlates of the extent of diffusivity changes were also tested. We found areas of significantly increased diffusivity (SID) in 13 patients. Eight had SID in the EZ, 9 within the irritative zone (IZ) and 12 outside, mainly in connected areas. We found a correlation between the extent of SID and the duration of epilepsy (p corrected=0.026, R =0.621). In addition, SID was significantly less widespread in negative-MRI patients (p =0.028). However, we found no significant differences concerning either seizure frequency (p =0.302), seizure generalization (p =0.841), history of status (p =0.396), or surgical outcome (p =0.606). We suggest that SID in normal appearing areas is not a specific signature of epileptogenicity in FLE, and is more likely to reflect multifactorial and potentially evolving neuro-glial injuries. [Copyright &y& Elsevier]

The aim of this work was to study the dosimetric potential of the Monte Carlo code MCNPX applied to the protontherapy field. For series of clinical configurations a comparison between simulated and experimental data was carried out, using the proton beam line of the MEDICYC isochronous cyclotron installed in the Centre Antoine Lacassagne in Nice. The dosimetric quantities tested were depth-dose distributions, output factors, and monitor units. For each parameter, the simulation reproduced accurately the experiment, which attests the quality of the choices made both in the geometrical description and in the physics parameters for beam definition. These encouraging results enable us today to consider a simplification of quality control measurements in the future. Monitor Units calculation is planned to be carried out with preestablished Monte Carlo simulation data. The measurement, which was until now our main patient dose calibration system, will be progressively replaced by computation based on the MCNPX code. This determination of Monitor Units will be controlled by an independent semi-empirical calculation. [ABSTRACT FROM AUTHOR]

Abstract: Presurgical evaluation of frontal lobe epilepsy (FLE) remains a challenging issue and frequently requires invasive depth electrode recording. In this study, we aimed at evaluating the potential usefulness of a non-invasive technique such as proton magnetic resonance spectroscopic imaging (1H-MRSI) in the presurgical evaluation of FLE and at investigating the potential electrophysiological correlates of the metabolic disturbances as defined by 1H-MRSI. We compared the distribution of 1H-MRSI abnormalities with the electrophysiological abnormalities defined by stereo-electroencephalography (SEEG) recording in 12 patients presenting with several subtypes of FLE. We also used 12 control subjects in order to obtain normative 1H-MRSI data. We used a multilevel 1H-MRSI protocol to better sample the principal regions of the frontal lobe. We also applied a metabolic mapping technique allowing a visual display of metabolic data. A significant decrease of both N-acetyl-aspartate/phosphocreatine-creatine and N-acetyl-aspartate/(choline-compounds + phosphocreatine-creatine) ratios was observed in regions involved in the epileptogenic zone (EZ) and/or the irritative zone (IZ) compared to regions without electrical abnormalities in the same patients (P = 0.044 and P = 0.018, respectively), and also compared to controls (P = 0.004 and P = 0.0001, respectively). No significant differences in metabolic ratios were observed between those regions involved in the EZ and those involved in the IZ only. Our results suggest a link between the relative decrease of N-acetyl-aspartate and the EZ as well as the IZ in FLE. Thus, multilevel 1H-MRSI protocol may add pertinent information during the non-invasive presurgical evaluation of FLE. [Copyright &y& Elsevier]

Abstract: Objective: We present a novel quantitative method to statistically analyze the distribution of multichannel intracerebral interictal spikes (multi-IIS) in stereoelectroencephalographic (SEEG) recordings. The method automatically extracts groups of brain structures conjointly and frequently involved in the generation of interictal activity. These groups are referred to as ‘subsets of co-activated structures’ (SCAS). We applied the method to long duration interictal recordings in patients with mesial temporal lobe epilepsy (MTLE) and analyzed the reproducibility of subsets of structures involved in the generation of multi-IIS for each patient and among patients. Methods: Fifteen patients underwent long-term intracerebral EEG recording (SEEG technique) using depth electrodes. A 1h period of continuous interictal EEG recording was selected for each patient with precautions regarding the time after anesthesia pre-SEEG, the temporal distance with respect to seizures, the vigilance state of the patient, and the anti-epileptic drug withdrawal. A research of SCAS was conducted on each recording using the developed method that includes 3 steps: (i) automatic detection of monochannel intracerebral interictal spikes (mono-IIS), (ii) formation of multi-IIS using a temporal sliding window, and (iii) extraction of SCAS. In the third step, statistical tests are used to evaluate the frequency of multi-IIS as well as their significance (with respect to the ‘random distribution of mono-IIS’ case). Results: In each patient, several thousands of multi-IIS (mean±SD, 3322±2190) were formed and several SCAS (mean±SD, 3.80±1.47) were automatically extracted. Results show that reproducible subsets of brain structures are involved in the generation of interictal activity. Although SCAS were found to be variable from one patient to another, some invariant information was pointed up. In all patients, multi-IIS distribute over two distinct groups of structures: mesial structures (15/15) and lateral structures (7/15). Moreover, two particular structures, the internal temporal pole and the temporo-basal cortex, may be conjointly involved with either the first or the second group. Finally, some extracted SCAS seem to match well-defined anatomo-functional circuits of the temporal lobe. Conclusions and Significance: During interictal activity in MTLE, similar subsets of temporal lobe structures are involved in the generation of spikes. This paper brings statistical evidence for the existence of these subsets and presents a method to automatically extract them from SEEG recordings. Interictal activity is spatially organized in the temporal lobe and preferentially involves two functional systems of the temporal lobe (either mesial or lateral). [Copyright &y& Elsevier]

Purpose: We recorded with intracerebral electrodes the onset of limbic seizures in patients with mesial temporal lobe epilepsy (MTLE) to identify the dynamic interactions between the hippocampus (HIP), amygdala (AMY) and entorhinal cortex (EC). Method: Interactions were quantified by analyzing the interdependencies between stereo-electroencephalographic (SEEG) signals using a nonlinear cross-correlation method. Seizures from 12 patients were analyzed by identifying three periods of interest: (i) the rapid discharge that occurs at seizure onset (“during rapid discharge”, DRD period); (ii) the time interval that precedes this rapid discharge (“before rapid discharge”, BRD period); and the time that follows the rapid discharge (“after rapid discharge”, ARD period). The transition from interictal to ictal discharge was classified into: (i) “type 1 transition” in which the emergence of pre-ictal spiking was followed by a rapid discharge; and (ii) “type 2 transition” that was associated with rapid discharge onset without prior spiking. Results: In both types of transition the BRD period was characterized by significant cross-correlation values indicating strong interactions among mesial temporal structures as compared to those seen during background activity. Interactions between HIP and EC were predominant in 10 of 12 patients (83%). Interactions between EC and AMY were observed in 6 of 12 cases (50%) and between AMY and HIP in 7 of 12 cases (58%). Analysis of coupling directionality indicated that most of the couplings were driven either by HIP (six patients) or by the EC (four patients). The DRD period was characterized by a significant decrease of cross-correlation values. In addition, type 1 transition was characterized by interactions that uniformly involved the three structures, while type 2 transition was associated with interactions between EC and HIP. Finally, analysis of coupling direction demonstrated that the HIP was always the leader in type 1 transition whereas in type 2 the EC was most often the leading structure. Conclusions: This study demonstrates that pre-ictal synchronization between mesial structures is the initial event for seizures starting in the mesial temporal region. [Copyright &y& Elsevier]

Research in brain-damaged patients has suggested that the right hemisphere plays a role in unilateral spatial neglect (USN), but provides only limited information for pinpointing the intraparietal localization of the lesions associated with this syndrome. We report a case of unilateral neglect in a patient who underwent a right inferior parietal cortectomy for refractory epilepsy without any macroscopic lesion. We describe the evolution of the neuropsychological disturbances observed at 3 and 24 months after cortectomy. This case illustrates the role played by the inferior parietal lobe and, particularly, the parietal opercule in USN syndrome, and provides strong “experimental” evidence of the special role played by the inferior parietal lobule in the perception processes related to spatial attention. [Copyright &y& Elsevier]

Purpose: To evaluate the independent prognostic factors for survival, metastasis, local recurrence, and enucleation in patients who had undergone proton-beam therapy for posterior uveal melanomas.Design: Interventional case series.Methods: In this retrospective study, 224 consecutive incident cases were treated at the Biomedical Cyclotron Centre (Nice, France) from June 1991 to December 1997. Overall, metastasis-free, local recurrence-free, and enucleation-free survival rates were calculated according to the Kaplan-Meier method using the log-rank test. The multivariate prognostic analysis was performed using the Cox proportional hazards model.Results: The 5-year overall survival rate was 78.1% (SE: 3.7%). A largest basal tumor diameter (LTD) below 10 mm and female sex were independently associated with a better prognosis. The 5-year metastasis-free survival rate was 75.6% (SE: 3.6%). Only an LTD above 10 mm and ciliary body involvement were independently associated with metastasis. Ten patients (4.5%) had a local recurrence, which was correlated with the risk of metastasis (P = .045). The 5-year enucleation-free survival rate was 69.6% (SE: 4.0%). Once again, an LTD below 10 mm and female sex were predictive of a better prognosis.Conclusion: Our results with proton-beam therapy correspond to those reported in the literature. This treatment strategy is safe and yields predictably good results. In addition to the two independent prognostic factors for survival and metastasis, namely LTD and ciliary body involvement, sex also had a significant impact in our case series, but the clinical relevance of this finding is unknown. [Copyright &y& Elsevier]

Objective: Our main goal was to evaluate the accuracy of an original non-supervised spatio-temporal magnetoencephalography (MEG) localization method used to characterize interictal spikes generators.Methods: MEG and stereotactic intracerebral recordings (stereo-electro-encephalographic exploration, SEEG) data were analyzed independently in 4 patients. MEG localizations were performed with and without anatomical constraints.Results: We analyzed 1326 interictal spikes recorded using MEG. For each patient, 2–3 typical source patterns were described. These source configurations were compared with SEEG. SEEG findings and MEG spatio-temporal localization results were remarkably coherent in our 4 patients. Most of the MEG patterns were similar to interictal SEEG patterns from a spatio-temporal point of view.Conclusions: We were able to evaluate the usefulness of our non-invasive localization method. This approach described correctly the part of the epileptogenic network involved in the generation of interictal events. Our results demonstrate the potential of MEG in the non-invasive spatio-temporal characterization of generators of interictal spikes. [Copyright &y& Elsevier]

Abstract This paper focuses on high-frequency (gamma band) EEG activity, the most characteristic electrophysiological pattern in focal seizures of human epilepsy. It starts with recent hypotheses about: (i) the behaviour of inhibitory interneurons in hippocampal or neocortical networks in the generation of gamma frequency oscillations; (ii) the nonuniform alteration of GABAergic inhibition in experimental epilepsy (reduced dendritic inhibition and increased somatic inhibition); and (iii) the possible depression of GABAA,fast circuit activity by GABAA,slow inhibitory postsynaptic currents. In particular, these hypotheses are introduced in a new computational macroscopic model of EEG activity that includes a physiologically relevant fast inhibitory feedback loop. Results show that strikingly realistic activity is produced by the model when compared to real EEG signals recorded with intracerebral electrodes. They show that, in the model, the transition from interictal to fast ictal activity is explained by the impairment of dendritic inhibition. [ABSTRACT FROM AUTHOR]

It has been demonstrated that botulinum toxin type A (BTX-A) injections reduce spasticity and improve muscle growth in children with spasticity. It has been postulated that BTX-A allows the learning of more normal movement patterns. The aim of this study was to measure the effect of this treatment on functional ability, as measured by the Gross Motor Function Measure (GMFM), in children with spastic hemiplegic cerebral palsy. Children of 3–13 years and meeting the selection criteria were randomly allocated to the control or injection group using a matched pair design. A match constituted a child within 6 months of age with the same Modified Ashworth Score (MAS) for the gastroc-soleus and within 10% of the same goal scores on the Gross Motor Function Measure. Twelve matched pairs were enrolled. Outcomes were measured on enrolment and at 1, 3 and 6 months post injection. The time course of the response to BTX-A was assessed with measurements of the MAS, dynamic range of motion (R1) and static muscle length (R2). Motor function was assessed using the 88-item GMFM and parental satisfaction with a 10-point visual analogue scale. Within pair comparisons of the GMFM using the Wilcoxon signed rank test indicated that the treatment group made significantly greater gains than controls at 3 months (P=0.02) with even greater differences seen at 6 months (P=0.004). Using parametric statistics, the intrapair difference in proportional change of GMFM increased from 35% (4 to 65) at 3 months to 52% (17–87) at 6 months. Response to injection was confirmed by a decrease in MAS in the treatment group and very little change in controls. This difference was significant (P=0.002) at 3 months and was attenuated but still significant (P=0.016) at 6 months; the difference in proportional change decreased from 44% at 3 months to 22% at 6 months. Changes in R1 reflected those of MAS in the treatment group and deteriorated significantly over the study period in controls. Parents of children in the treatment group were more satisfied than controls, but satisfaction scores did not correlate with changes in function or technical outcomes suggesting that this may be a placebo effect. The changes in GMFM correlated with changes in technical outcomes at 3 months, suggesting a causal relationship. The intrapair differences in GMFM continued to increase even after the local response to injection had started to wane. [ABSTRACT FROM AUTHOR]

Characterizes the absence epilepsy by an atypical electroencephalography pattern during sleep in France. Persistence of seizures at a late age; Consideration of drug resistance; Visibility of social and learning handicaps.

Abstract. In the field of epilepsy, the analysis of stereoelectroencephalographic (SEEG, intra-cerebral recording) signals with signal processing methods can help to better identify the epileptogenic zone, the area of the brain responsible for triggering seizures, and to better understand its organization. In order to evaluate these methods and to physiologically interpret the results they provide, we developed a model able to produce EEG signals from "organized" networks of neural populations. Starting from a neurophysiologically relevant model initially proposed by Lopes Da Silva et al. [Lopes da Silva FH, Hoek A, Smith H, Zetterberg LH (1974) Kybernetic 15: 27-37] and recently re-designed by Jansen et al. [Jansen BH, Zouridakis G, Brandt ME (1993) Biol Cybern 68: 275-283] the present study demonstrates that this model can be extended to generate spontaneous EEG signals from multiple coupled neural populations. Model parameters related to excitation, inhibition and coupling are then altered to produce epileptiform EEG signals. Results show that the qualitative behavior of the model is realistic; simulated signals resemble those recorded from different brain structures for both interictal and ictal activities. Possible exploitation of simulations in signal processing is illustrated through one example; statistical couplings between both simulated signals and real SEEG signals are estimated using nonlinear regression. Results are compared and show that, through the model, real SEEG signals can be interpreted... [ABSTRACT FROM AUTHOR]

Rational: Epilepsies associated to Hypothalamic Hamartomas are frequently drug-resistant with a severe psychiatric and cognitive comorbidity. We have organized a prospective trial in order to evaluate the safety and efficacy of radiosurgery using the Gamma Knife (GK). Material and Method: Between January 1999 and December 2007, 64 patients were investigated, included and treated by GK in Timone University Hospital. Preoperative work-up and 3 years evaluation included: seizure diary, neuropsychological testing, psychiatric evaluation, endocrinological evaluation, visual field and acuity. Till now, follow up of more than 3 years is available for 40 patients. The hamartomas were of topological Type I (Regis et al ) in 8 patients, Type II in 14 patients, Type III in 12 patients, Type IV in 1 patients, Type V in 1 patients and mixed Type in 3 patients. The median of the marginal dose was 17 Gy (Mean: 17,8+-1,6 ; min=14; max= 20). The median of the volume was 419 mm3 (Mean 556,7 +- 394; min=31 ; max=1600). The median number of isocenters was 8 (Mean 9,4 +-5,5; min=1 ; max= 31). 25 patients (62,5%) have been treated twice due to partial result. Results: The median follow up was 62 months (36-107). At last follow up the rate of Engel I was 47,5 %, Engel II 17,5% (I+II 65%) & Engel III (20%). Global Psychiatric and Cognitive comorbidity was considered cured in 28%, improved 56%, stable 8% and have continued to worsen in 8%. No permanent neurological (specially no mnesic nor visual deficit) side effect is reported. A non-disabling transient poikilothermia was observed in 3 patients (7,5%). A transient increase of seizure frequency is reported in 7 patients (17,5%). Microsurgery was proposed due to insufficient efficacy of GKS in 5 patients (Type II, Type III, type IV in one patient each, mixed type in 2 patients). The postoperative outcome (after GK and microsurgery) was Engel I (40%), Engel III (40%) and Engel IV (20%). Conclusion: This prospective trial is demonstrating the very good safety efficacy of Gamma Knife radiosurgery in the long term. Beyond seizure reduction, the improvement of the psychiatric, cognitive condition and school and social insertion is turning out to be the major benefit of GKS in this frequently catastrophic epilepsy group. Disclosure: No significant relationships. [ABSTRACT FROM AUTHOR]