piperidines and Epilepsy--Temporal-Lobe

The application of PET with NMPB has provided useful information toward understanding the pathogenesis of mesial TLE, and can be used as a tool in the presurgical evaluation. Many other patient populations have yet to be studied with cholinergic neuroreceptor imaging. The use of NAChR radioligands in the study of ADNFLE may be especially rewarding.

Topics: Benzilates; Brain; Calcium Channel Blockers; Epilepsy, Temporal Lobe; Flumazenil; GABA Modulators; Humans; Piperidines; Receptors, Cholinergic; Tomography, Emission-Computed

Opioids are known to stimulate surface electroencephalographic activity in patients with temporal lobe epilepsy. The objective of the current study was to compare the electrocorticographic activation effects of the newer short-acting opioid remifentanil with those of alfentanil during epilepsy surgery under general anaesthesia.. Thirteen patients undergoing temporal lobe epilepsy surgery under general anaesthesia received alfentanil 30 microg kg(-1) and remifentanil 1 microg kg(-1) as i.v. boluses in sequence. The design was a randomized double-blind cross-over study. After opening the dura, electrocorticogram (ECoG) electrode contact strips were placed over the temporal and supratemporal neocortex and depth electrodes were inserted in the amygdala and hippocampus. Alfentanil 30 microg kg(-1) or remifentanil 1 microg kg(-1) were administered randomly in a blinded fashion. The ECoG was recorded continuously before and after the injection of each drug. The interictal epileptiform activity (spikes and sharp waves) above baseline was analysed.. Both drugs increased epileptiform activity especially that recorded from depth electrodes in the temporal limbic structures. No epileptiform activity was recorded from the electrodes overlying the supratemporal neocortex before or after drug administration. The more potent activator was alfentanil, which caused an increase in activation from baseline of 99.8% compared with 67.4% for remifentanil. In addition, alfentanil activated the epileptiform activity in 3 patients in which remifentanil had no effect. There were no changes in heart rate after the opioid boluses. Both remifentanil and alfentanil caused significant reductions in blood pressure at 3 and 5 min after administration.. We conclude that at the doses used in this study, alfentanil is the better opioid for intraoperative activation of the ECoG in neurosurgical patients undergoing resection of a temporal lobe epileptic focus. This pharmacological activation of epileptiform activity assists in localizing and confirming the site of surgical excision. Neither alfentanil nor remifentanil activated epileptiform activity in non-epileptic brain tissue.

Topics: Adult; Alfentanil; Analgesics, Opioid; Anesthesia, General; Cross-Over Studies; Double-Blind Method; Electroencephalography; Epilepsy, Temporal Lobe; Female; Hemodynamics; Humans; Intraoperative Care; Male; Middle Aged; Piperidines; Remifentanil

Therapies for epilepsy mainly provide symptomatic control of seizures since most of the available drugs do not target disease mechanisms. Moreover, about one-third of patients fail to achieve seizure control. To address the clinical need for disease-modifying therapies, research should focus on targets which permit interventions finely balanced between optimal efficacy and safety. One potential candidate is the brain-specific enzyme cholesterol 24-hydroxylase. This enzyme converts cholesterol to 24S-hydroxycholesterol, a metabolite which among its biological roles modulates neuronal functions relevant for hyperexcitability underlying seizures. To study the role of cholesterol 24-hydroxylase in epileptogenesis, we administered soticlestat (TAK-935/OV935), a potent and selective brain-penetrant inhibitor of the enzyme, during the early disease phase in a mouse model of acquired epilepsy using a clinically relevant dose. During soticlestat treatment, the onset of epilepsy was delayed and the number of ensuing seizures was decreased by about 3-fold compared to vehicle-treated mice, as assessed by EEG monitoring. Notably, the therapeutic effect was maintained 6.5 weeks after drug wash-out when seizure number was reduced by about 4-fold and their duration by 2-fold. Soticlestat-treated mice showed neuroprotection of hippocampal CA1 neurons and hilar mossy cells as assessed by post-mortem brain histology. High throughput RNA-sequencing of hippocampal neurons and glia in mice treated with soticlestat during epileptogenesis showed that inhibition of cholesterol 24-hydroxylase did not directly affect the epileptogenic transcriptional network, but rather modulated a non-overlapping set of genes that might oppose the pathogenic mechanisms of the disease. In human temporal lobe epileptic foci, we determined that cholesterol 24-hydroxylase expression trends higher in neurons, similarly to epileptic mice, while the enzyme is ectopically induced in astrocytes compared to control specimens. Soticlestat reduced significantly the number of spontaneous seizures in chronic epileptic mice when was administered during established epilepsy. Data show that cholesterol 24-hydroxylase contributes to spontaneous seizures and is involved in disease progression, thus it represents a novel target for chronic seizures inhibition and disease-modification therapy in epilepsy.

Topics: Animals; Cholesterol; Cholesterol 24-Hydroxylase; Disease Models, Animal; Epilepsy; Epilepsy, Temporal Lobe; Hippocampus; Humans; Mice; Piperidines; Pyridines; RNA; Seizures

Temporal lobe epilepsy (TLE) is defined as the sporadic occurrence of spontaneous recurrent seizures, and its pathogenesis is complex. SHP-2 (Src homology 2-containing protein tyrosine phosphatase 2) is a widely expressed cytosolic tyrosine phosphatase protein that participates in the regulation of inflammation, angiogenesis, gliosis, neurogenesis and apoptosis, suggesting a potential role of SHP-2 in TLE. Therefore, we investigated the expression patterns of SHP-2 in the epileptogenic brain tissue of intractable TLE patients and the various effects of treatment with the SHP-2-specific inhibitor SHP099 on a pilocarpine model. Western blotting and immunohistochemistry results confirmed that SHP-2 expression was upregulated in the temporal neocortex of patients with TLE. Double-labeling experiments revealed that SHP-2 was highly expressed in neurons, astrocytes, microglia and vascular endothelial cells in the epileptic foci of TLE patients. In the pilocarpine-induced C57BL/6 mouse model, SHP-2 upregulation in the hippocampus began one day after status epilepticus, reached a peak at 21 days and then maintained a significantly high level until day 60. Similarly, we found a remarkable increase in SHP-2 expression at 1, 7, 21 and 60 days post-SE in the temporal neocortex. In addition, we also showed that SHP099 increased reactive gliosis, the release of IL-1β, neuronal apoptosis and neuronal loss, while reduced neurogenesis and albumin leakage. Taken together, the increased expression of SHP-2 in the epileptic zone may be involved in the process of TLE.

Topics: Adolescent; Adult; Animals; Brain; Convulsants; Disease Models, Animal; Epilepsy, Temporal Lobe; Female; Humans; Male; Mice; Mice, Inbred C57BL; Pilocarpine; Piperidines; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Pyrimidines; Up-Regulation; Young Adult

Patients with medically refractory epilepsy may benefit from resective epilepsy surgery. However even the best centers experience surgical failures. It is therefore important to find techniques that may aid in neurosurgical planning of epileptic focus resection. Recordings of electrical brain activity with EEG during seizures reveal abnormal cortical hypersynchronization. Between seizures the EEG often shows interictal depolarizing phenomena such as spikes reflecting an irritable focus of the brain. In the present study we investigated the effect of intravenous remifentanil on the spike activity in the temporal neocortex and hippocampus. We examined 65 patients with mesial temporal lobe epilepsy during surgery, prior to resection. We used a 20-lead grid on the cortex and a 4-lead strip in the lateral ventricle on the hippocampus. At least two 3-min periods of ECoG were recorded - before and after remifentanil injection. In a number of patients we examined the effect of repeated injections in order to estimate the dose-response curve. We describe a significant effect of remifentanil on the average spike activity with an increment from 16 spikes per minute at baseline to 36 spikes per minute after remifentanil injection (p<0.0001). The increase in spike activity was typically seen after 40-50s. When mu-receptors were antagonized with a preceding injection of naloxone, spike activity increased 25% in response to remifentanil as opposed to 80% when remifentanil was preceded by placebo. In only seven out of 59 patients did the injection of remifentanil change the topographic location of the spike focus. Typically administration of remifentanil led to a focus of increased spike count. Activity in other areas was suppressed making the focus stand out from the background. Our observation that remifentanil potentiates spike activity is in agreement with previous findings from smaller studies. Furthermore, we were able to describe the pharmacodynamics of the remifentanil effect on spike activity. Peri-operative provocation with remifentanil may play a future role in guiding neurosurgical intervention during epilepsy resection surgery.

Topics: Adolescent; Adult; Analgesics, Opioid; Brain Mapping; Brain Waves; Child; Child, Preschool; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy, Temporal Lobe; Female; Humans; Infant; Male; Middle Aged; Neurosurgical Procedures; Piperidines; Remifentanil; Retrospective Studies; Young Adult

Epileptic seizures are short episodes of abnormal brain electrical activity. Many survivors of severe epilepsy display delayed neuronal death and permanent cognitive impairment. Donepezil is an acetylcholinesterase inhibitor and is an effective treatment agent for Alzheimer's disease. However, the role of donepezil in seizure-induced hippocampal injury remains untested. Temporal lobe epilepsy (TLE) was induced by intraperitoneal injection of pilocarpine (25 mg/kg). Donepezil (2.5 mg/kg/day) was administered by gavage in three different settings: (1) pretreatment for three days before the seizure; (2) for one week immediately after the seizure; and (3) for three weeks from three weeks after the seizure. We found that donepezil showed mixed effects on seizure-induced brain injury, which were dependent on the treatment schedule. Pretreatment with donepezil aggravated neuronal death, oxidative injury, and microglia activation. Early treatment with donepezil for one week showed neither adverse nor beneficial effects; however, a treatment duration of three weeks starting three weeks after the seizure showed a significant reduction in neuronal death, oxidative injury, and microglia activation. In conclusion, donepezil has therapeutic effects when injected for three weeks after seizure activity subsides. Therefore, the present study suggests that the therapeutic use of donepezil for epilepsy patients requires a well-conceived strategy for administration.

Topics: Animals; Cell Death; Cholinesterase Inhibitors; Disease Models, Animal; Donepezil; Drug Administration Schedule; Epilepsy, Temporal Lobe; Hippocampus; Indans; Male; Neurons; Nootropic Agents; Oxidative Stress; Pilocarpine; Piperidines; Rats, Sprague-Dawley; Seizures

Epilepsy is a chronic disorder characterized by spontaneous recurrent seizures. Brain inflammation is increasingly recognized as a critical factor for seizure precipitation, but the molecular mediators of such proconvulsant effects are only partly understood. The chemokine CCL2 is one of the most elevated inflammatory mediators in patients with pharmacoresistent epilepsy, but its contribution to seizure generation remains unexplored. Here, we show, for the first time, a crucial role for CCL2 and its receptor CCR2 in seizure control. We imposed a systemic inflammatory challenge via lipopolysaccharide (LPS) administration in mice with mesial temporal lobe epilepsy. We found that LPS dramatically increased seizure frequency and upregulated the expression of many inflammatory proteins, including CCL2. To test the proconvulsant role of CCL2, we administered systemically either a CCL2 transcription inhibitor (bindarit) or a selective antagonist of the CCR2 receptor (RS102895). We found that interference with CCL2 signaling potently suppressed LPS-induced seizures. Intracerebral administration of anti-CCL2 antibodies also abrogated LPS-mediated seizure enhancement in chronically epileptic animals. Our results reveal that CCL2 is a key mediator in the molecular pathways that link peripheral inflammation with neuronal hyperexcitability.. Substantial evidence points to a role for inflammation in epilepsy, but currently there is little insight as to how inflammatory pathways impact on seizure generation. Here, we examine the molecular mediators linking peripheral inflammation with seizure susceptibility in mice with mesial temporal lobe epilepsy. We show that a systemic inflammatory challenge via lipopolysaccharide administration potently enhances seizure frequency and upregulates the expression of the chemokine CCL2. Remarkably, selective pharmacological interference with CCL2 or its receptor CCR2 suppresses lipopolysaccharide-induced seizure enhancement. Thus, CCL2/CCR2 signaling plays a key role in linking systemic inflammation with seizure susceptibility.

Topics: Animals; Antibodies; Benzoxazines; Chemokine CCL2; Disease Models, Animal; Electroencephalography; Epilepsy, Temporal Lobe; Excitatory Amino Acid Agonists; Hippocampus; Indazoles; Inflammation; Kainic Acid; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Piperidines; Propionates; Receptors, CCR2; RNA, Messenger; Signal Transduction; Up-Regulation

A growing bulk of evidence suggests that cannabinoid system plays a pivotal role in the control of hyperexcitability phenomena. Notwithstanding, the anticonvulsant action of cannabinoids has not been fully addressed, in particular the involvement of potential cellular neuromodulators, for instance nitric oxide. In the current study, we focused on two distinct rat models of temporal lobe epilepsy, the Maximal Dentate Activation and the pilocarpine-induced acute seizures, providing both electrophysiological and behavioral data on cannabinoid and nitrergic system interplay. We evaluated the antiepileptic effects of WIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN), a CB agonist, and of 7-Nitroindazole (7NI), a preferential neuronal nitric oxide synthase (nNOS) inhibitor, at different doses, alone and in combination. MDA study showed that these drugs protected animals in a dose-dependent manner from electrically induced epileptiform discharges. In pilocarpine model, a dose-related activity of 7NI and WIN: a) decreased the behavioral scoring, used to describe the severity of chemically induced acute seizures; b) affected latency of the onset of acute convulsions; c) dampened mortality rate. Interestingly, the combination of the treatments brought to light that individually ineffective doses of WIN turn into effective when nNOS activity is pharmacologically inhibited in both experimental conditions. This effect is mediated by CB1 receptor since the co-administration of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251), a CB1 receptor specific antagonist, thwarted the 7NI-WIN convergent action. In the light of this, our findings suggest a putative antagonism between CBr-activated pathway and NO signaling in the context of neuronal hyperexcitability and contribute to elucidate possible synaptic processes underlying neuroprotective properties of cannabinoids, with a view to better integrate antiepileptic therapy.

Topics: Animals; Benzoxazines; Cannabinoid Receptor Agonists; Cannabinoids; Disease Models, Animal; Dose-Response Relationship, Drug; Epilepsy, Temporal Lobe; Hippocampus; Indazoles; Male; Morpholines; Naphthalenes; Nitric Oxide; Nitric Oxide Synthase; Pilocarpine; Piperidines; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1

Patients with temporal lobe epilepsy (TLE) often suffer from comorbid psychiatric diagnoses such as depression, anxiety, or impaired cognitive performance. Endocannabinoid (eCB) signaling is a key regulator of synaptic neurotransmission and has been implicated in the mechanisms of epilepsy as well as several mood disorders and cognitive impairments.. We employed a pilocarpine model of TLE in C57/BJ mice to investigate the role of eCB signaling in epileptogenesis and concomitant psychiatric comorbidities.. We sought to alter the neuronal levels of a known eCB receptor ligand, 2-arachidonylglycerol (2-AG), through the use of RHC80267 or JZL184. Pilocarpine-treated mice were treated with RHC80267 (1.3 μmol) or JZL184 (20 mg/kg) immediately after the termination of status epilepticus (SE), which was followed by daily treatment for the next 7 days. Our results indicated that RHC80267 treatment significantly reduced the percentage of mice suffering from spontaneous recurrent seizures (SRS) in addition to decreasing the duration of observed seizures when compared to vehicle treatment. Furthermore, RHC80267 attenuated depression and anxiety-related behaviors, improved previously impaired spatial learning and memory, and inhibited seizure-induced hippocampal neuronal loss during the chronic epileptic period. In contrast, JZL184 administration markedly increased the frequency and the duration of observed SRS, enhanced the previously impaired neuropsychological performance, and increased hippocampal damage following SE.. These findings suggest that RHC80267 treatment after the onset of SE could result in an amelioration of the effects found during the chronic epileptic period and yield an overall decrease in epileptic symptoms and comorbid conditions. Thus, alterations to endocannabinoid signaling may serve as a potential mechanism to prevent epileptogenesis and manipulation of this signaling pathway as a possible drug target.

Topics: Animals; Anticonvulsants; Benzodioxoles; Cyclohexanones; Disease Models, Animal; Electroencephalography; Epilepsy, Temporal Lobe; Exploratory Behavior; Hindlimb Suspension; Hippocampus; Male; Maze Learning; Mice; Mice, Inbred C57BL; Neurodegenerative Diseases; Piperidines

Hippocampal sclerosis, the main pathological sign of chronic temporal lobe epilepsy (TLE), is associated with oxidative injury, altered N-methyl d-aspartate receptor (NMDAR) stoichiometry, and loss of hippocampal neurons. However, the mechanisms that drive the chronic progression of TLE remain elusive. Our previous studies have shown that NADPH oxidase activation and ERK 1/2 phosphorylation are required for the up-regulation of the predominantly pre-synaptic NR2B subunit auto-receptor in both in vitro and in vivo pilocarpine (PILO) models of TLE. To provide further understanding of the cellular responses during the early-stages of hyper excitability, we investigated the role of oxidative damage and altered NR2B functions. In rat primary hippocampal cultures, we found that N-acetylcysteine (NAC) prevented PILO-mediated thiol oxidation, apoptosis, cell death and NR2B subunit over-expression. Interestingly, NAC did not block thiol oxidation when added to the neurons 6h after the PILO exposure, suggesting that disulfide formation could rapidly become an irreversible phenomenon. Moreover, NAC pre-treatment did not prevent PILO-induced NR2A subunit over-expression, a critical event in hippocampal sclerosis. Pre-treatment with the highly specific NR2B subunit inhibitor, ifenprodil, partially decreased PILO-mediated thiol oxidation and was not effective in preventing apoptosis and cell death. However, if acutely administered 48h after PILO exposure, ifenprodil blocked glutamate-induced aberrant calcium influx, suggesting the crucial role of NR2B over-expression in triggering neuronal hyper-excitability. Furthermore, ifenprodil treatment was able to prevent NR2A subunit over-expression by means of ERK1/2 phosphorylation. Our findings indicate oxidative stress and NR2B/NMDA signaling as promising therapeutic targets for co-treatments aimed to prevent chronic epilepsy following the seizure onset.

Topics: Acetylcysteine; Animals; Apoptosis; Cells, Cultured; Disease Models, Animal; Dizocilpine Maleate; Epilepsy, Temporal Lobe; Excitatory Amino Acid Antagonists; Hippocampus; Male; MAP Kinase Signaling System; Neurons; Neuroprotective Agents; Oxidation-Reduction; Oxidative Stress; Pilocarpine; Piperidines; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Sulfhydryl Compounds

Activation of the neurokinin-1 (NK1) receptor by neuropeptide substance P (SP) induces and maintains epileptic activity in various experimental models of epilepsy. The primary objective of this study was to investigate whether neurobiological changes linked to NK1-SP receptor system are associated with hyperexcitability in patients with temporal lobe epilepsy (TLE). A secondary objective was to investigate the relationship between seizure frequency and NK1 receptor availability.. A positron emission tomography study was conducted with the selective NK1 receptor antagonist [(11)C]GR205171 in nine patients with TLE and 18 healthy control participants. Parametric PET images were generated using the Patlak graphical method, with cerebellum as reference region. Data analyses including group comparisons were performed using statistical parametric mapping.. Patients with TLE showed increased NK1 receptor availability in both hemispheres with the most pronounced increase in anterior cingulate gyrus ipsilateral to seizure onset. A positive correlation between NK1 receptor availability and seizure frequency was observed in the medial temporal lobe and in the lentiform nucleus ipsilateral to the seizure onset.. Our results suggest that there is an intrinsic network using the NK1-SP receptor system for synaptic transmission and epileptiform activity in TLE.

Topics: Adult; Carbon Radioisotopes; Epilepsy, Temporal Lobe; Female; Humans; Male; Middle Aged; Neurokinin-1 Receptor Antagonists; Piperidines; Positron-Emission Tomography; Receptors, Neurokinin-1; Severity of Illness Index; Substance P; Temporal Lobe; Tetrazoles; Young Adult

Traditionally, intraoperative intracranial electroen-cephalography-recordings are limited to the detection of the irritative zone defined by interictal spikes. However, seizure patterns revealing the seizure onset zone are thought to give better localizing information, but are impractical due to the waiting time for spontaneous seizures. Therefore, provocation by seizure precipitants may be used with the precaution that spontaneous and provoked seizures may not be identical.. We present evidence that hyperventilation induced and drug induced focal seizures may arise from different brain regions in the same patient.. Hyperventilation and ultra short acting opioid remifentanil were used separately as intraoperative precipitatants of seizure patterns, while recording from subdural and intraventricular electrodes in a patient with temporal lobe epilepsy. Two different ictal onset zones appeared in response to hyperventilation and remifentanil. Both zones were resected and the patient has remained essentially seizure free for 1 year. Furthermore, this is the first description of hyperventilation used as an intraoperative seizure precipitant in human focal epilepsy.

Topics: Anesthetics, Intravenous; Cerebral Cortex; Child; Electroencephalography; Epilepsy, Temporal Lobe; Female; Humans; Hyperventilation; Intraoperative Care; Piperidines; Remifentanil

To assess the value of remifentanil in intraoperative evaluation of spike activity in patients undergoing surgery for mesial temporal lobe epilepsy (MTLE).. Twenty-five patients undergoing temporal lobectomy for medically intractable MTLE were enrolled in the study. Electrocorticography (ECoG) recordings were performed on the intraventricular hippocampus and from the anterior inferior temporal and lateral neocortex before and after a 300 microg intravenous bolus of remifentanil. Spike activity was quantified as spike-count per minute.. A significant increase (P < 0.005) in spike activity was observed after administration of remifentanil in 23 of 25 patients (92%). Furthermore, two patients who did not have any spike activity on the baseline ECoG developed spikes after administration of remifentanil.. The results suggest that remifentanil can enhance spike activity in the epileptogenic zone and reveal otherwise concealed epileptogenic tissue in patients with MTLE. Thus, remifentanil may prove to be an important diagnostic tool during surgical treatment for intractable focal epilepsy.

Topics: Adolescent; Adult; Anesthetics, Intravenous; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy, Temporal Lobe; Female; Humans; Male; Middle Aged; Monitoring, Intraoperative; Piperidines; Psychosurgery; Remifentanil; Statistics, Nonparametric

The use of remifentanil for sedation during awake epilepsy surgery has been described in a case report. However, little information is available regarding the effect of remifentanil on the quality of intraoperative electrocorticography (ECoG). This study was designed to investigate the effect of sedative doses of remifentanil on ECoG interictal spike activity among patients undergoing awake anterior temporal lobectomy for refractory epilepsy. Ten adult patients were studied prospectively. After baseline EcoG recordings were obtained, remifentanil was administered as a continuous infusion at 0.1 microg/kg/min and the ECoG recorded continuously for 15 minutes. Recordings obtained before and during the administration of remifentanil were compared with respect to spike frequency and location. A trend toward a small decrease in spike frequency was observed as patients became increasingly somnolescent and background ECoG activity slowed. The difference was not statistically significant. Blood pressure and heart rate were not adversely affected by the administration of remifentanil. Respiratory rates decreased in all patients (mean decrease, 8 breaths/min) and one patient transiently developed a respiratory rate of 4 breaths per minute that elicited a decrease in the rate of remifentanil administration. Remifentanil administered at sedation doses does not adversely affect intraoperatively recorded interictal spike activity. Further investigation of the use of this drug during awake epilepsy surgery is warranted.

Topics: Adult; Cerebral Cortex; Conscious Sedation; Consciousness; Electroencephalography; Epilepsy, Temporal Lobe; Female; Humans; Hypnotics and Sedatives; Infusions, Intravenous; Male; Monitoring, Intraoperative; Piperidines; Prospective Studies; Remifentanil

High-dose i.v. opioids (e.g., alfentanil, 50 microg/kg bolus) are known to increase the intraoperative reading of epileptiform activity during epilepsy surgery (ES), thereby facilitating localization of the epileptogenic zone (i.e., the site of ictal onset and initial seizure propagation). However, this phenomenon has not been studied with remifentanil (i.e., a novel ultra-short acting opioid). The purpose of the present study was to evaluate the effect of remifentanil on electrocorticography (ECoG) during ES.. After Institutional Review Board approval, 25 adult patients undergoing elective ECoG-guided anterior temporal corticectomy were enrolled. At the time of ECoG, anesthesia consisted of inhaled isoflurane < or =0.1% (end-tidal) in 50% N2O, and i.v. fentanyl, 2 microg/kg/h and vecuronium. Patients were maintained at normocapnia and normoxia during ECoG. After acquisition of baseline ECoG, bolus remifentanil, 2.5 microg/kg i.v., was administered. The number of epileptiform spikes occurring 5 min before and after this bolus were compared by using a one-sided sign test; p values < or =0.05 were considered statistically significant.. When compared with baseline ECoG, bolus i.v. remifentanil significantly increased the frequency of single spikes or repetitive spike bursts in the epileptogenic zone while suppressing activity in surrounding normal brain.. During ES, remifentanil enhanced epileptiform activity during intraoperative ECoG. Such observations facilitate localization of the epileptogenic zone while minimizing resection of nonepileptogenic eloquent brain tissue. Although not specifically evaluated in this study, we speculate that remifentanil's short elimination half-life will facilitate neurologic function testing immediately after ES. Should this be the case, we envision remifentanil has the potential to supplant other opioids (e.g., alfentanil) during ECoG-guided ES.

Topics: Adult; Aged; Brain Mapping; Cerebral Cortex; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Epilepsy, Temporal Lobe; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Monitoring, Intraoperative; Neurologic Examination; Piperidines; Psychosurgery; Remifentanil; Temporal Lobe

Topics: Adolescent; Adult; Drug Synergism; Electroencephalography; Epilepsy, Temporal Lobe; Epilepsy, Tonic-Clonic; Ethosuximide; Humans; Male; Middle Aged; Nitriles; Phenothiazines; Phenytoin; Piperidines; Tranquilizing Agents

Topics: Adolescent; Adult; Aged; Amygdala; Astrocytoma; Brain Neoplasms; Central Nervous System Diseases; Cerebral Cortex; Chronic Disease; Electroencephalography; Electrophysiology; Epilepsy, Temporal Lobe; Female; Humans; Male; Mental Disorders; Middle Aged; Parasympatholytics; Piperidines; Temporal Lobe