Biomedical subjects

Vincent Navarro

Publications and source records attributed to Vincent Navarro.

12 recordsLinked to original sources

PubMed2006

Seizure anticipation: are neurophenomenological approaches able to detect preictal symptoms?

Analysis of electroencephalographic signals and several brain imaging studies suggest that a preictal state precedes the onset of seizures. In this study, we used phenomenological strategies to detect modifications in patients' experience before their seizures. We observed that patients with partial epilepsy feeling an aura (n=9) frequently experienced prodromes (n=6). Prodromes were subtle preictal symptoms, varying among patients and having common negative features. They were generally continuous before seizures and could last hours, whereas auras were sudden and intermittent. All patients were able to recognize facilitating factors. We also found that patients spontaneously develop cognitive countermeasures to avoid facilitating factors (n=6), to prevent a seizure (n=1) or to interrupt a seizure (n=5). Prodromes are not specific enough for clinical use, but could refine the behavioral strategies used in the treatment of epilepsy and the pathophysiology of the preictal state.

Adult↗

PubMed2006

Toothbrush-thinking seizures.

Seizures associated with toothbrushing have been reported in patients with precentral or postcentral partial epilepsy. Seizures precipitated by thinking have been described in patients with idiopathic generalized epilepsy. We report a patient with intractable partial epilepsy in which seizures were induced both by toothbrushing, and by seeing or thinking about toothbrush and toothpaste. Video-EEG analysis revealed a left temporal lobe origin for these reflex seizures. We discuss how complex multimodal stimuli may trigger these reflex seizures.

Electroencephalography↗

PubMed2005

On the intrinsic time scales involved in synchronization: a data-driven approach.

We address the problem of detecting, from scalar observations, the time scales involved in synchronization of complex oscillators with several spectral components. Using a recent data-driven procedure for analyzing nonlinear and nonstationary signals [Huang, Proc. R. Soc. London A 454, 903 (1998)], we decompose a time series in distinct oscillation modes which may display a time varying spectrum. When applied to coupled oscillators with multiple time scales, we found that motions are captured in a finite number of phase-locked oscillations. Further, in the synchronized state distinct phenomena as phase slips, anti-phase or perfect phase locking can be simultaneously observed at specific time scales. This fully data-driven approach (without a priori choice of filters or basis functions) is tested on numerical examples and illustrated on electric intracranial signals recorded from an epileptic patient. Implications for the study of the build-up of synchronized states in nonstationary and noisy systems are pointed out.

Biophysics↗

PubMed2005

Seizure anticipation: do mathematical measures correlate with video-EEG evaluation?

PURPOSE: Analysis of the EEG signal has recently shown evidence of dynamic changes preceding ictal onset in seizures selected from patients with clear epileptogenic foci. Most of the studies were conducted in highly selected EEG epochs and patients. In addition, these studies relied mostly on mathematical approaches and neglected clinical and visual EEG parameters. We therefore performed a systematic comparison of a nonlinear method (the similarity measure) with classic visual inspection of the EEG and the patient's clinical state. METHODS: We analyzed the dynamics of long epochs of intracranial EEG containing 129 electroclinical and 45 electrographic seizures in 13 successive unselected patients undergoing presurgical evaluation. RESULTS: (a) The similarity measure detected preictal dynamical changes of the EEG signal in two thirds of the seizures whether or not a clear focus was identified, and whether seizures were electroclinical or purely electrographic. The mean duration of preictal changes was 12 min. (b) The preictal changes were correlated with various visually detectable EEG changes in 78.9% of electroclinical seizures. (c) 81.5% of the preictal dynamic changes were correlated with changes of vigilance or behavior. (d) Fluctuations of the dynamics were not necessarily followed by seizures. CONCLUSIONS: Our results indicate that EEG dynamics frequently change before seizures. These preictal changes are most often associated with the EEG changes accompanying transitions between states of vigilance. The preictal dynamic changes may represent physiologic changes acting as facilitating factors or pathologic changes reflecting a network dysfunction.

Adolescent↗

PubMed2004

Preictal state identification by synchronization changes in long-term intracranial EEG recordings.

OBJECTIVE: There is accumulated evidence that mesial temporal lobe seizures are preceded by a preictal transition that evolves over minutes to hours. In the present study, we investigated these possible preictal changes in long-term intracranial recordings of five patients by a measure of phase synchronization. In order to clearly distinguish preictal changes from all the other interictal states, we developed an automatic extraction of representative patterns of interictal synchronization activity. This reference library was used to classify the successive synchronization patterns of long-term recordings into groups of similar patterns. Altered states of brain synchronization were identified as deviating from patterns in the reference library and were evaluated relative to the times of seizure onset in terms of sensitivity and specificity. METHODS: A phase-locking measure was estimated using a sliding window analysis on 15 frequency bands (2Hz steps between 0 and 30Hz), for all pairs of EEG channels in the epileptogenic temporal lobe (14-20 channels), over the entire data sets (total analyzed duration 305h). The preictal identification encompasses three basic stages: (1) a preprocessing stage involving the determination of a reference library of characteristic interictal synchronization patterns using a K-means algorithm, and the identification of discriminant variables differentiating interictal from preictal states, (2) a classification stage of the synchronization pattern via a minimum Mahalanobis distance to the reference patterns, as well as detection of outliers, (3) an evaluation stage of the sensitivity and specificity of the detection by receiver-operating characteristic curves. RESULTS: In most of the cases (36 of 52 seizures, i.e. 70%), a specific state of brain synchronization can be observed several hours before the actual seizure. The changes involved both increases and decreases of the synchronization levels, occurring mostly within the 4-15Hz frequency band, and were often localized near the primary epileptogenic zone. CONCLUSIONS: The analysis of phase synchronization offers a way to distinguish between a preictal state and normal interictal activity. These findings suggest that brain synchronizations are preictally altered in the epileptogenic temporal lobe, inducing a pathological state of higher susceptibility for seizure activity. SIGNIFICANCE: Phase synchronization is capable of extracting information from the EEG that allow the definition of a preictal state. Although the proposed analysis does not constitute genuine seizure anticipation, these changes in neuronal synchronization may provide helpful information for prospective seizure warning.

Brain Mapping↗

PubMed2004

Radioimmunotherapy of prostate cancer in human xenografts using monoclonal antibodies specific to prostate specific membrane antigen (PSMA): studies in nude mice.

BACKGROUND: Prostate specific membrane antigen (PSMA), expressed by virtually all prostate cancers is an ideal target for targeted therapy of prostate cancer. Radiolabeled J591 monoclonal antibody (MAb) binds with high affinity to an extracellular epitope of PSMA and localizes specifically in PSMA positive LNCaP tumors in vivo. METHODS: Pre-clinical radioimmunotherapy (RIT) studies using (131)I-huJ591 and (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)-huJ591 MAbs were studied in nude mice bearing LNCaP xenografts. RESULTS: A 15-90% reduction in mean tumor volume was observed after a single dose of (131)I-huJ591 (3.7-11.1 MBq) or (90)Y-DOTA-huJ591 (3.7-7.4 MBq). The median survival time increased 2-3 times relative to untreated controls. Multiple administrations of fractionated doses of (90)Y-DOTA-huJ591 were even more effective with minimal toxicity. Radiation dose to blood and tumor was higher with (90)Y than with (131)I. The maximum tolerated dose (MTD) is 5.55 MBq for (90)Y-DOTA-huJ591 and more than 11.1 MBq for (131)I-huJ591. For (90)Y-DOTA-huJ591 at MTD, dose to the tumor was 2,753 cGy. CONCLUSIONS: In nude mice bearing PSMA positive tumors, radiation dose to the tumor with (90)Y-DOTA-J591 is greater for large tumors than with (131)I-J591. The theoretical and practical considerations strongly suggest that (90)Y-DOTA-huJ591 may be a suitable radiopharmaceutical for the treatment of prostate cancer.

Animals↗

PubMed2003

Mesial temporal lobe epilepsy: a pathological replay of developmental mechanisms?

Focal epilepsies of the mesial temporal lobe are often associated with a hippocampal sclerosis. Changes in Cl homeostasis and GABAergic signalling in downstream regions, may contribute to the human pathology. A review of changes in cellular and synaptic function and connectivity after de-afferentation suggests this epileptic syndrome may involve a pathological replay of developmental mechanisms.

Animals↗

PubMed2003

Spatio-temporal dynamics prior to neocortical seizures: amplitude versus phase couplings.

The mechanisms underlying the transition of brain activity toward epileptic seizures remain unclear. Based on nonlinear analysis of both intracranial and scalp electroencephalographic (EEG) recordings, different research groups have recently reported dynamical smooth changes in epileptic brain activity several minutes before seizure onset. Such preictal states have been detected in populations of patients with mesial temporal lobe epilepsy (MTLE) and, more recently, with different neocortical partial epilepsies (NPEs). In this paper, we are particularly interested in the spatio-temporal organization of epileptogenic networks prior to seizures in neocortical epilepsies. For this, we characterize the network of two patients with NPE by means of two nonlinear measures of interdependencies. Since the synchronization of neuronal activity is an essential feature of the generation and propagation of epileptic activity, we have analyzed changes in phase synchrony between EEG time series. In order to compare the phase and amplitude dynamics, we have also studied the degree of association between pairs of signals by means of a nonlinear correlation coefficient. Recent findings have suggested changes prior to seizures in a wideband frequency range. Instead, for the examples of this study, we report a significant decrease of synchrony in the focal area several minutes before seizures (>>30 min in both patients) in the frequency band of 10-25 Hz mainly. Furthermore, the spatio-temporal organization of this preictal activity seems to be specifically related to this frequency band. Measures of both amplitude and phase coupling yielded similar results in narrow-band analysis. These results may open new perspectives on the mechanisms of seizure emergence as well as the organization of neocortical epileptogenic networks. The possibility of forecasting the onset of seizures has important implications for a better understanding, diagnosis and a potential treatment of the epilepsy.

Adult↗

PubMed2003

Toward a neurodynamical understanding of ictogenesis.

Although considerable information on cellular and network mechanisms of epilepsy exists, it is still not understood why, how, and when the transition from interictal to ictal state takes place. The authors review their work on nonlinear EEG analysis and provide consistent evidences that dynamical changes in the neural activity allows the characterization of a preictal state several minutes before seizure onset. This new neurodynamical approach of ictogenesis opens new perspectives for studying the basic mechanisms in epilepsy as well as for possible therapeutic interventions.

Brain↗

PubMed2003

Radiolabeled monoclonal antibodies specific to the extracellular domain of prostate-specific membrane antigen: preclinical studies in nude mice bearing LNCaP human prostate tumor.

UNLABELLED: Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein, is highly expressed by virtually all prostate cancers. PSMA is also expressed on the tumor vascular endothelium of virtually all solid carcinomas and sarcomas but not on normal vascular endothelium. PSMA is currently the focus of several diagnostic and therapeutic strategies. We have previously reported on the radiolabeling and in vitro binding properties of monoclonal antibodies (mAbs) (J415, J533, and J591) that recognize and bind with high affinity to the extracellular domain of PSMA (PSMA(ext)). This article reports on the in vivo behavior and tumor uptake of (131)I- and (111)In-labeled antiPSMA(ext) mAbs (J415, J533, and J591) and their potential utility for radioimmunotherapy. METHODS: In nude mice bearing PSMA-positive human LNCaP tumors, the pharmacokinetics, biodistribution, and tumor uptake of these antibodies was compared with (111)In-7E11 mAb, specific to the intracellular domain of PSMA (PSMA(int)). Autoradiographic studies were done to identify intratumoral distribution of radiolabeled mAbs. RESULTS: With (131)I-labeled antibodies, the net tumor retention of radioactivity by day 6 was significantly higher with J415 (15.4% +/- 1.1%) and 7E11 (14.5% +/- 1.7%) than with J591 (9.58% +/- 1.1%). By contrast, the tumor uptake of (111)In-1,4,7,10-tetraazacyclododecane-N,N',N", N"'-tetraacetic acid-labeled J415 and J591 gradually increased with time and was quite similar to that of 7E11. In addition, the blood clearance of (111)In-labeled J415 and J591 antibodies was relatively faster than that of radiolabeled 7E11. As a consequence, the tumor-to-blood ratios with J415 and J591 were higher than that of 7E11. The localization of radiolabeled anti-PSMA(ext) antibodies in PSMA-positive LNCaP tumors was highly specific because the tumor uptake of (131)I-labeled J415 and J591 was more than twice that of a nonspecific antibody. Furthermore, the tumor uptake of (131)I-J591 was almost 20 times higher in PSMA-positive LNCaP tumors than in PSMA-negative PC3 and DU145 tumor xenografts. Autoradiographic studies suggested that 7E11 (anti-PSMA(int)) distinctly favors localization to areas of necrosis whereas J415 and J591 (anti-PSMA(ext)) demonstrated a distinct preferential accumulation in areas of viable tumor. CONCLUSION: These results clearly demonstrate that PSMA-specific internalizing antibodies such as J415 and J591 may be the ideal mAbs for the development of novel therapeutic methods to target the delivery of beta-emitting radionuclides ((131)I, (90)Y, and (177)Lu) for the treatment of PSMA-positive tumors. In addition, because J591 and J415 mAbs are specific to PSMA(ext), thus targeting viable tumor, these immunoconjugates are better candidates for targeted radioimmunotherapy than are antibodies targeting PSMA(int).

Animals↗

PubMed2002

On the origin of interictal activity in human temporal lobe epilepsy in vitro.

The origin and mechanisms of human interictal epileptic discharges remain unclear. Here, we describe a spontaneous, rhythmic activity initiated in the subiculum of slices from patients with temporal lobe epilepsy. Synchronous events were similar to interictal discharges of patient electroencephalograms. They were suppressed by antagonists of either glutamatergic or gamma-aminobutyric acid (GABA)-ergic signaling. The network of neurons discharging during population events comprises both subicular interneurons and a subgroup of pyramidal cells. In these pyramidal cells, GABAergic synaptic events reversed at depolarized potentials. Depolarizing GABAergic responses in neurons downstream to the sclerotic CA1 region contribute to human interictal activity.

Action Potentials↗

PubMed2002

Seizure anticipation in human neocortical partial epilepsy.

The transition of brain activity towards an epileptic seizure is still a poorly understood phenomenon. Dynamic changes in brain activity have been detected several minutes before seizure emergence in populations of patients with mesial temporal lobe epilepsy (MTLE), using non-linear analysis of intracranial EEG recordings. Similar detection of a pre-ictal state has been obtained with standard scalp EEG recordings using a modified non-linear method. Here we applied this strategy to the seizures of patients with neocortical partial epilepsy. Results obtained by non-linear similarity analysis of 41 seizures from 11 patients with refractory partial epilepsy originating from various sites of the neocortex showed that (i) a pre-ictal state was detected in 90% of the patients and in 83% of the seizures whatever their location, with a mean anticipation time of 7.5 min; (ii) similar pre-ictal dynamic changes were detected when non-linear analysis methods were applied to either intracranial or scalp EEG recordings; (iii) the recording sites exhibiting these pre-ictal changes were distributed both within the epileptogenic focus and at remote locations; (iv) most pre-ictal dynamic changes were not correlated with linear changes in the frequency spectrum or with changes in the visually inspected EEG and the patients' behaviour. Hypotheses on the neuronal mechanisms underlying the pre-ictal period are discussed. The present results, together with those recently obtained in an MTLE population, suggest that changes in pre-ictal dynamics are a general phenomenon associated with seizure emergence in a wide population of patients with partial epilepsy, wherever the epileptogenic focus is located. The possibility of anticipating the onset of seizures has considerable therapeutic implications.

Adolescent↗