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P Chauvel

Publications and source records attributed to P Chauvel.

At least 19 recordsLinked to original sources

[Analysis of ocular surface alterations following proton beam radiation in eyes with conjunctival malignant melanoma].

BACKGROUND: In cases of large, diffuse or multilocular growth pattern of conjunctival melanoma, proton beam irradiation can serve as an alternative therapy to exenteration. In extended tumours, ocular surface problems can result after therapy. In this study we examined ocular surface integrity of ten patients who underwent proton beam radiation between 1996 and 2002. METHODS: The patients were examined during their follow-up. Eight of the ten cases who underwent proton radiotherapy were recurrent tumours, which were previously treated with other adjuvant therapies. We performed a standard ophthalmological examination and detailed tear film diagnostics. RESULTS: The follow-up was 17-87 months (mean: 40.9+/-20.1). In six cases more than 50% of the upper and lower eyelids were included in the radiation field. All of these cases showed moderate to severe sicca symptoms. The impression cytology revealed squamous metaplasia of conjunctival cells in nine of ten cases. CONCLUSIONS: Squamous metaplasia of conjunctival epithelia indicates a radiogenic, persisting disturbance of differentiation of the conjunctival epithelial cells. The tear film instability correlates with the loss of mucin-secreting goblet cells and meibomian gland dysfunction.

Adult↗

1H-MRS imaging in intractable frontal lobe epilepsies characterized by depth electrode recording.

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 ((1)H-MRSI) in the presurgical evaluation of FLE and at investigating the potential electrophysiological correlates of the metabolic disturbances as defined by (1)H-MRSI. We compared the distribution of (1)H-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 (1)H-MRSI data. We used a multilevel (1)H-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 (1)H-MRSI protocol may add pertinent information during the non-invasive presurgical evaluation of FLE.

Adolescent↗

Auditory evoked potential patterns to voiced and voiceless speech sounds in adult developmental dyslexics with persistent deficits.

Auditory evoked potentials (AEPs) were recorded from eight developmental dyslexic adults with persistent reading, spelling and phonological deficits, and 10 non-dyslexic controls to voiced (/ba/) and voiceless (/pa/) consonant-vowel syllables. Consistent with previous data, non-dyslexics coded these stimuli differentially according to the temporal cues that form the basis of the voiced/voiceless contrast: AEPs had time-locked components with latencies that were determined by the temporal structure of the stimuli. Dyslexics were characterized by one of two electrophysiological patterns: AEP pattern I dyslexics demonstrated a differential coding of stimuli on the basis of some temporal cues, but with an atypically large number of components and a considerable delay in AEP termination time; AEP pattern II dyslexics demonstrated no clear differential coding of stimuli on the basis of temporal cues. These data reveal the presence of anomalies in cortical auditory processing which could underlie persistent perceptual and linguistic impairments in some developmental dyslexics. Furthermore, scalp AEP distribution maps showing the difference observed between /ba/ and /pa/ activity over time suggest that the regions implicated in the processing of crucial time-related acoustic cues were not systematically lateralized to the left hemisphere like they were for non-dyslexics. These findings may be conducive to a better understanding and treatment of perceptual dysfunctions in developmental language disorders.

Acoustic Stimulation↗

A method to identify reproducible subsets of co-activated structures during interictal spikes. Application to intracerebral EEG in temporal lobe epilepsy.

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 1 h 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).

Adolescent↗

[Spatio-temporal dynamics of neuronal networks in partial epilepsy].

INTRODUCTION: The anatomo-functional organization of partial drug-resistant epilepsies is the subject of much current research aiming at better understanding these pathologies and improving their treatment. The work carried out by our team on the study of intracerebral recording falls within this category of research. The objectives are to identify the neural networks involved in the generation of paroxysmal activity and to understand their spatio-temporal dynamics, in order to be able in the long term to propose targeted therapeutic approaches likely to "control" these networks. STATE OF ART: The traditional concept of epileptic "focus" must nowadays be replaced by a more complex model taking into account potential interactions within the neural networks involved in the seizure. Indeed, during partial seizures, involved cerebral structures are the site of characteristic oscillations which may be synchronized or on the contrary transiently desynchronized. These epileptic rhythms may disturb the physiological rhythms underlying normal cognitive processes; these cognitive processes may thus be impaired in partial epilepsy, even those remote from the site of origin of the discharge. In this article we describe a model of organization of human partial seizures, through characterization of the relationships ("synchrony") between intracerebral signals recorded in the involved structures. We propose that seizures are generated in an initial network of highly epileptogenic brain structures (epileptogenic zone network, EZN) whose activity is synchronized; this activity is then transiently desynchronized with the appearance of fast oscillations. During a second ictal phase, other cortical and subcortical structures are the seat of slower rhythmic modifications that are synchronized (propagation network, PN). The emergence of a particular clinical semiology in the course of the seizure depends on these phenomena which can in certain cases "mimic" a normal cerebral process or on the contrary provoke a major rupture in normal cerebral functioning. CONCLUSIONS: These studies contribute to improvement in our knowledge of the neural networks involved in partial epilepsies. In the future, this type of research may contribute to the development of specific treatments that target certain pathophysiological mechanisms involved in seizure generation.

Brain↗

Monte Carlo simulation of a protontherapy platform devoted to ocular melanoma.

Patients with ocular melanoma have been treated since June 1991 at the medical cyclotron of the Centre Antoine Lacassagne (CAL). Positions and sizes of the ocular nozzle elements were initially defined based on experimental work, taking as a pattern functional existing facilities. Nowadays Monte Carlo (MC) calculation offers a tool to refine this geometry by adjusting size and place of beam modeling devices. Moreover, the MC tool is a useful way to calculate the dose and to evaluate the impact of secondary particles in the field of radiotherapy or radiation protection. Both LINAC and cyclotron producing x rays, electrons, protons, and neutrons are available in CAL, which suggests choosing MCNPX for its particle versatility. As a first step, the existing installation was input in MCNPX to check its aptitude to reproduce experimentally measured depth-dose profile, lateral profile, output-factor (OF), and absolute dose. The geometry was defined precisely and described from the last achromatic bending magnet of our proton beam line to the position of treated eyes. Relative comparisons of percentage depth-dose and lateral profiles, performed between measured data and simulations, show an agreement of the order of 2% in dose and 0.1 mm in range accuracy. These comparisons, carried out with and without beam-modifying device, yield results compatible to the required precision in ocular melanoma treatments, as long as adequate choices are made on MCNPX input decks for physics card. Absolute dose and OF issued from calculations and measurements were also compared. Results obtained for these two kinds of data, carried out in the simplified situation of an unmodulated beam, indicate that MC calculation could effectively complement measurements. These encouraging results are a large source of motivation to promote further studies, first in a new design of the ocular nozzle, and second in the analysis of the influence of beam-modifying devices attached to the final patient collimator, such as wedge or compensators, on dose values.

Computer Simulation↗

Cortical stimulation study of the role of rhinal cortex in déjà vu and reminiscence of memories.

OBJECTIVE: To study the role of perirhinal (PC) and entorhinal cortices (EC) in dreamy state symptoms (déjà vu and reminiscence of scenes). These phenomena have been attributed to functional alteration of memory networks supported by the medial temporal lobes, principally involving the amygdala and hippocampus. The role of sub-hippocampal structures (EC and PC) in inducing these phenomena has not previously been addressed. METHODS: The authors studied the symptoms evoked by direct electrical stimulations of PC and EC in comparison with those obtained after stimulation of the amygdala and hippocampus. Stimulations were performed in a group of 24 patients with epilepsy, during stereoelectroencephalographic (SEEG) recordings in the setting of presurgical evaluation. All patients had electrodes that sampled the rhinal cortices, amygdala, and hippocampus. RESULTS: A total of 280 stimulations were analyzed. Entorhinal and perirhinal stimulations induced classic mesial temporal lobe responses (emotional, dysautonomic) but also more specific responses, particularly the déjà vu phenomenon and reminiscence of scenes. Such déjà vu or déjà vécu type responses were produced proportionately more often by stimulation of the EC than by stimulation of the amygdala and hippocampus. In particular, déjà vu was associated with stimulation of the EC and reminiscence of memories with PC stimulation. CONCLUSION: This study strongly suggests that experiential symptoms are largely dependent upon functional modification of the physiology of the rhinal cortices.

Adult↗

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.

Adolescent↗

Survival after proton-beam irradiation of uveal melanomas.

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.

Adult↗

Short-latency components of evoked potentials to median nerve stimulation recorded by intracerebral electrodes in the human pre- and postcentral areas.

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.

Adolescent↗

Unilateral spatial neglect following right inferior parietal cortectomy.

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.

Epilepsy↗

[Ciliary body melanomas. Survival and prognostic aspects after brachytherapy or proton therapy].

INTRODUCTION: Our main goals were to study the survival of patients with uveal melanomas involving the ciliary body 5 and 10 years after treatment and to review prognosis. MATERIAL AND METHODS: This study investigated 106 tumors (27 ciliary body melanomas and 79 choroidal-ciliary melanomas) of patients treated between June 1983 and April 1998. Seventy-two patients were treated with 106-ruthenium applicators and 34 were treated with proton therapy. Some large tumors or recurrences required a second treatment. The mean follow-up period was 91 months. RESULTS: The mean tumor sizes before treatment were 6,6mm for melanoma thickness and 10.3mm for mean largest basal melanoma diameters (LTD). Of the patients studied, 71% were still alive at 5 years, 35% had metastasis and 27.7% developed recurrences. Multivariate analysis showed that the risk factors for melanoma-related death were LTD greater than 13mm, presence of exudative retinal detachment, macroscopic iris root involvement at the time of diagnosis, and choroidal-ciliary location. DISCUSSION AND CONCLUSION: With 71% of patients still alive at 5 years, this review shows that melanomas involving the ciliary body do not seem less severe than more posterior uveal tumors. Because of size differences between ciliary body melanomas and choroidal-ciliary melanomas, we cannot come to the conclusion that choroidal-ciliary melanomas have a poorer prognosis than ciliary body melanomas. Largest tumor diameter over 13mm, presence of exudative retinal detachment, and macroscopic iris root involvement at the time of diagnosis are important risk factors for melanoma-related death, as shown by the multivariate analysis.

Adolescent↗

[EEG and video-EEG explorations in refractory partial epilepsy].

The assessment of drug -resistant partial epilepsy by electrophysiological explorations (based on non-invasive EEG) involves two types of analysis: the study of the seizures, primarily by video-EEG exploration, and the study of interictal activities based on visual analysis, and in some centers on techniques of source localization (high resolution EEG and magnetoencephalography, MEG). Seizure recording can be used to confirm the focal nature and the epileptic origin of the seizure as well as other features such as severity (secondary generalization, frequency, falls etc.). In the pre-surgical approach, the video-EEG recordings enable study of the electro-clinical correlations and allow assumptions on the anatomical localization of the epileptogenic zone. Precise analysis of the localization of the interictal activities (especially within the framework of extra-temporal epilepsies) based on source localization methods, makes it possible to put forth assumptions on the localization of the irritative zone.

Anticonvulsants↗

[2003 update of Standards, Options and Recommandations for radiotherapy for patients with salivary gland malignant tumors (excluding lymphona, sarcoma and melanoma)].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers. and specialists from French public universities,general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVES: To update clinical practice guidelines for the management of patients with salivary gland malignant tumors previously validated in 1997. These recommendations cover diagnosis, treatment and follow-up of patients with these tumors. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been defined, the document is submitted for review by independent reviewers. RESULTS: This article presents the updated clinical practice guidelines concerning irradiation of patient with salivary gland tumors. The main recommendations are: 3 dimensional conformal radiotherapy (with or without intensity modulation) or 2D irradiation can be used; for surgical complete resected patients, postoperative photon radiotherapy should not be used in case of low grade stage I and 11 tumors(standard, level of evidence B2) but should be used for high grade stage II, II and IV tumors and for low grade stage III and IV tumors(standard, level of evidence B2). Neutron therapy should not be used in all of these cases (standard, level of evidence D); for patients presenting an incomplete macroscopic or microscopic surgical residual disease, postoperative irradiation must be delivered(standard). Neutron or photon therapy can be either delivered (options); for non operable patients neutron or photon therapy can be either delivered (options, level of evidence B2); for unresectable tumors or in case of recurrent neoplasms, exclusive neutron therapy or surgical tumor reduction combined with postoperative photon beam irradiation can be proposed (options, level of evidence C).

Combined Modality Therapy↗

Non-supervised spatio-temporal analysis of interictal magnetic spikes: comparison with intracerebral recordings.

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.

Adolescent↗

Epileptic fast intracerebral EEG activity: evidence for spatial decorrelation at seizure onset.

Low-voltage rapid discharges (or fast EEG ictal activity) constitute a characteristic electrophysiological pattern in focal seizures of human epilepsy. They are characterized by a decrease of signal voltage with a marked increase of signal frequency (typically beyond 25 Hz). They have long been observed in stereoelectroencephalographic (SEEG) signals recorded with intra-cerebral electrodes, generally occurring at seizure onset and simultaneously involving distinct brain regions. Spectral properties of rapid ictal discharges as well as spatial correlations measured between SEEG signals generated from distant sites before, during and after these discharges were studied. Cross-correlation estimates within typical EEG sub-bands and statistical tests performed in 10 patients suffering from partial epilepsy (frontal, temporal or fronto-temporal) reveal that SEEG signals are significantly de-correlated during the discharge period compared with periods that precede and follow this discharge. These results can be interpreted as a functional decoupling of distant brain sites at seizure onset followed by an abnormally high re-coupling when the seizure develops. They lead to the concept of 'disruption' that is complementary of that of 'activation' (revealed by significantly high correlations between signals recorded during seizures), both giving insights into our understanding of pathophysiological processes involved in human partial epilepsies as well as in the interpretation of clinical semiology.

Adolescent↗

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.

Brain Diseases↗

Dose-response effect of levetiracetam 1000 and 2000 mg/day in partial epilepsy.

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 > or = 50 and > or = 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 (> or = 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.

Adolescent↗