piperidines and Epilepsies--Partial

Magnetoencephalography (MEG) provides source localization of interictal spikes. We use total intravenous anesthesia (TIVA) with propofol to immobilize uncooperative children. We evaluate the effect of TIVA on interictal spikes in children who have intractable epilepsy with or without MRI lesions.. We studied 28 children (3-14 years; mean, 6.6). We intravenously administered propofol (30-60 microg/kg/min) to record MEG with simultaneous EEG. We evaluated MEG spike sources (MEGSSs). We compared spikes on simultaneous EEG under TIVA with those on scalp video-EEG without TIVA.. There was a significant decrease in frequent spikes (10 patients, 36%) on simultaneous EEG under TIVA compared to those (22 patients, 79%) on scalp video-EEG without TIVA (P<0.01). MEGSSs were present in 21 (75%) of 28 patients. Clustered MEGSSs occurred in 15 (83%) of 18 lesional patients but in 3 (30%) of 10 nonlesional patients (P<0.05). MEGSSs were more frequently absent in nonlesional (6 patients, 60%) than lesional (one patient, 5%) patients (P<0.01). Thirteen patients with MRI and/or histopathologically confirmed neuronal migration disorder most frequently showed clustered MEGSSs (11 patients, 85%) compared to those of other lesional and nonlesional patients.. Propofol-based TIVA reduced interictal spikes on simultaneous EEG. TIVA for MEG still had utility in identifying spike sources in a subset of pediatric patients with intractable epilepsy who were uncooperative and surgical candidates. In lesional patients, MEG under TIVA frequently localized the clustered MEGSSs. Neuronal migration disorders were intrinsically epileptogenic and produced clustered MEGSSs under TIVA. Nonlesional patients often had no MEGSS under TIVA.

Topics: Action Potentials; Adolescent; Anesthesia, Intravenous; Anesthetics, Intravenous; Brain; Brain Mapping; Child; Child, Preschool; Electroencephalography; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Female; Humans; Magnetic Resonance Imaging; Magnetoencephalography; Male; Piperidines; Propofol; Remifentanil; Seizures

Topics: Anesthesia, Intravenous; Atracurium; Biopsy; Carcinoma, Squamous Cell; Epilepsies, Partial; Hernia, Hiatal; Humans; Laryngeal Neoplasms; Laryngectomy; Male; Middle Aged; Miller Fisher Syndrome; Monitoring, Intraoperative; Neck Dissection; Neuromuscular Blocking Agents; Piperidines; Propofol; Pulmonary Disease, Chronic Obstructive; Remifentanil; Secondary Prevention; Tracheostomy

The anticonvulsant effect of cannabinoids (CB) has been shown to be mediated by the activation of the CB(1) receptor. This study evaluates the anticonvulsant activity of (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN55,212-2, CB agonist) alone or preceded by the administration of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, selective CB(1) antagonist) in an experimental in vivo model of complex partial seizures (maximal dentate gyrus activation - MDA) in the rat. WIN55,212-2 (21mgkg(-1)) exerted an anticonvulsant effect, significantly reduced by the pre-treatment with AM251 (1mgkg(-1), 30 min interval). Surprisingly, AM251, administered alone at the same dose, failed to induce any modification in MDA responses. Our data suggest the involvement of the CB system in the inhibitory control of hyperexcitability phenomena in a model of acute partial epilepsy. Although the MDA model per se does not induce a basal activation of CB(1) receptors, as suggested by the lack of efficacy of AM251 when administered alone, the partial suppression of WIN55,212-2-induced effects in rats pre-treated with AM251 allows to hypothesise that the WIN55,212-2-induced antiepileptic effect is strictly linked to an increased CB(1) receptor activation or to the involvement of further receptor subtypes.

Topics: Animals; Anticonvulsants; Benzoxazines; Brain; Calcium Channel Blockers; Cannabinoid Receptor Modulators; Cannabinoids; Disease Models, Animal; Electric Stimulation; Epilepsies, Partial; Male; Morpholines; Naphthalenes; Piperidines; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1

Topics: Anti-Obesity Agents; Cannabinoid Receptor Antagonists; Comorbidity; Eating; Epilepsies, Partial; Epilepsy, Generalized; Humans; Male; Middle Aged; Obesity; Piperidines; Pyrazoles; Rimonabant

Cortical dysplasia (CD) is often associated with pharmacoresistant epilepsy. Previous studies showed increased expression of the NMDA receptor subunit NR2B in dysplastic and epileptic human neocortex. We tested the hypothesis that differential increase of NR2B constitutes an epileptogenic mechanism in humans. Dysplastic neocortex and lateral temporal lobe regions resected for treatment of pharmacoresistant seizures were processed for electrophysiological, histological, and immunocytochemical studies. Assignment to the "dysplastic" (n = 8) and "non-dysplastic" (n = 8) groups was based on histology. Neurons in "dysplastic" samples differentially stained for NR2B. Western blot (n = 6) showed an immunoreactive band for NR2B in three out of four "dysplastic" samples. Epileptiform field potentials (EFP) were elicited in vitro by omission of magnesium from the bath. EFP in "dysplastic" slices were characterized by multiple afterdischarges, occurring at a significantly higher repetition rate than EFP in non-dysplastic slices. The NR2B-specific NMDA receptor inhibitor ifenprodil (10muM) suppressed EFP in dysplastic slices. In non-dysplastic slices, burst repetition rate did not change with ifenprodil application. In both dysplastic and non-dysplastic slices, EFP were suppressed by a non-specific NMDAR antagonist (APV) or AMPA receptor antagonist (CNQX). These results provide additional evidence that the differential expression of NR2B in dysplastic human neocortex may play a role in the expression of in-situ epileptogenesis in human CD. NR2B may constitute a target for new diagnostic and pharmacotherapeutic approaches.

Topics: Adolescent; Adult; Child; Child, Preschool; Cortical Synchronization; Epilepsies, Partial; Excitatory Amino Acid Antagonists; Female; Humans; In Vitro Techniques; Infant; Male; Membrane Potentials; Middle Aged; Neocortex; Neurons; Patch-Clamp Techniques; Piperidines; Receptors, N-Methyl-D-Aspartate; Reference Values; Single-Blind Method; Statistics, Nonparametric

Here I have reviewed evidence from electron microscopic studies showing that each of several sustained limbic seizure syndromes is associated with a type of acute brain damage which is ultrastructurally indistinguishable from the brain damage induced by Glu and other excitotoxins. In addition, I have presented evidence that persistent stimulation of specific axonal tracts that use Glu as transmitter results in Glu-like excitotoxic degeneration of postsynaptic neurons innervated by such tracts. Phencyclidine and ketamine, which powerfully block the neurotoxicity of the Glu analog NMA, protect against seizure-related brain damage. This may be explained by either an anticonvulsant or antiexcitotoxic mechanism, or both. Recent evidence suggests that an excitotoxic mechanism (excessive activation of Glu/Asp receptors) may underlie both seizure-mediated and anoxic brain damage. The acute fulminating type of neuronal degeneration induced by Glu is a Na+ and Cl- but not Ca2+ dependent phenomenon. According to a recent study, however, Glu may induce neuronal necrosis not only by an acute Ca2+ independent process but by a more slowly evolving Ca2+ dependent process. If, as these data suggest, an excitotoxic mechanism underlies brain damage associated with anoxia and epilepsy, a better understanding of excitotoxic mechanisms may lead eventually to prophylactic approaches for preventing such forms of brain damage.

Topics: Action Potentials; Animals; Brain; Cell Survival; Chick Embryo; Cholinergic Fibers; Disease Models, Animal; Edema; Epilepsies, Partial; Folic Acid; Hippocampus; Hypoxia; Kainic Acid; Ketamine; Microscopy, Electron; Parasympathomimetics; Phencyclidine; Piperidines; Seizures; Synaptic Transmission; Thalamus