Background: Epilepsy is usually controlled, but not cured, with medication. However, over 30% of people with epilepsy do not have seizure control even with the best available medications. A new antiepileptic drug as adjunctive therapy for patients with partial onset seizures has been discovered. Perampanel (E2007) is an orally active, noncompetitive, and highly selective AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptor antagonist. AMPA receptor antagonist is a potential pharmacologic treatment for partial onset seizures by blocking excessive neuronal materials activation.[1] Perampanel was well tolerated and displayed favorable pharmacologic properties, including oral bioavailability and a long half-life in Phase I studies[2]. Perampanel has not been shown to interact with other ionotropic glutamate receptors and is without the behavioral phencyclidine-like adverse events that may be observed with some NMDA-receptors antagonists[3]. Objective: The aim of the meta-analysis is to demonstrate the magnitude of safety and efficacy of perampanel in treating the refractory partial onset seizures when compared to placebo. Methods: A systematic review of Randomized controlled trials (RCTs) of perampanel was conducted. An electronic literature was identified by searching Medline, Embase and the Cochrane database. The primary efficacy end points were the 50% responder rate and treatment emergent adverse effects (TEAS). The secondary efficacy end points were the percent change in seizure frequency per 28 days relative to pre-perampanel baseline and incidence of withdrawal. In order to compare perampanel and placebo, we used Revmen to calculate Odds Ratio (OR), Confidence intervals, Risk Ratio (RR) and Risk Differences (RD). Results: A total of five RCTs were included in the studies. During Phase II studies (labeled as studies 206[4] and 208[4]) 201 patients were involved. During Phase III studies (labeled as 304[1], 305[3] and 306[5]) 1331 patients were included. For 50% responder rate, the pooled odds ratio of 4mg, 8mg and 12mg perampanel compared with placebo was 1.76 [95%CI:1.15, 2.69], 2.26[95%CI:1.66, 3.08] and 2.11[95%CI:1.35, 3.32] respectively. The pooled odds ratio of perampanel for adverse events: headache 1.03 [95%CI : 0.79, 1.34] ; dizziness 3.48 [95%CI: 1.94, 6.24] ; somnolence 2.09 [95%CI: 1.39, 3.15] and fatigue 1.83 [95%CI: 1.23, 2.71] respectively. Conclusion: The pooled odds ratio suggested perampanel might be more effective than placebo comparing the 50% responder rate. However, the risks of the TEAs were higher in the perampanel group when comparing with the placebo group. The use of 12 mg perampanel was shown be highly related with dizziness and somnolence. / published_or_final_version / Pharmacology and Pharmacy / Master / Master of Medical Sciences

No description available.

The Prevalence of Epilepsy and Seizures in Subjects with Fetal Alcohol Spectrum Disorders. MSc Thesis, Queen’s University, Kingston, Ontario, Canada, May 2009. OBJECTIVE: Fetal alcohol spectrum disorders (FASD) is the umbrella term that describes the range of adverse developmental outcomes that occur in offspring as a consequence of maternal drinking during pregnancy. FASD has been associated with a large number of co-morbidities, including neurological disorders such as epilepsy. Epilepsy occurs in 0.6% of the population in Canada. The aim of this study was to evaluate the prevalence of epilepsy or seizure disorders in people who have been diagnosed with Fetal Alcohol Syndrome (FAS), partial Fetal Alcohol Syndrome (pFAS) or Alcohol Related Neurodevelopmental Disorder (ARND). METHODS: A retrospective chart review was conducted on all active charts (N=1063) at St. Michael’s Hospital (Toronto) and Glenrose Rehabilitation Hospital (Edmonton) FASD clinics. A total of 425 subjects between the ages of 2 to 49 were included in the analysis. The relationship between FASD diagnosis and other risk factors for co-occurrence of epilepsy and seizures (e.g. extent of exposure to alcohol and other drugs, type of birth, maternal history, and trauma) in subjects with FASD was also examined. Chi-square tests and multivariate multinomial logistic regression were used. RESULTS: Twenty-five (5.9%) individuals with FASD had a confirmed diagnosis of epilepsy, and 50 (11.8%) had at least one documented seizure episode, yielding an overall prevalence of 17.7% with a history of seizures in this population. Those with epilepsy or seizures were two times (Odds Ratio=2.27, 95% Confidence Interval=1.14-4.51, p<0.05) more likely to have an unnatural birth and those with epilepsy were three times (OR=3.41, 95% CI 1.11-10.5, p<0.05) more likely to have had an unnatural type of birth (breech, caesarean, forceps or vacuum) than those subjects with no history of seizures. None of the other risk factors examined were associated with a greater prevalence of epilepsy or seizures in subjects with FASD. These results indicate a remarkably high prevalence of epilepsy/seizures in the FASD population of two specialized FASD clinics compared with the general population. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2009-07-23 16:38:17.17

No description available.

ABSTRACT BACKGROUND: Disconnections in cortical-related networks, the neuronal circuits of higher-order brain operations (attention, cognition, memory and perception), are thought to underlie dysfunctions of conscious integration such as those seen in schizophrenia. More than 80% of the neurons that make up these complex systems are glutamatergic. Clinical and experimental evidence suggest that NMDA-type glutamate receptors are implicated in the pathophysiology of schizophrenia. Cognitive impairment and schizophrenia-like symptoms (hallucinations and psychosis) are produced in humans by the administration of a single subanaesthetic dose of ketamine, a non-competitive NMDAr antagonist like phencyclidine and MK-801. The neuronal mechanisms underlying transient disruption in NMDAr function remains unknown. / Disorders of cognition-related coherences of gamma frequency (30-80 Hz) oscillations between cortical areas are a major functional abnormality in schizophrenic patients. Ketamine and MK-801, non-competitive NMDA receptor antagonists, abnormally and dose-dependently increase the power of wake-related, spontaneously occurring gamma oscillations in the electro-encephalogram (EEG) of the rat neocortex and concomitantly induces abnormal behaviour relevant to schizophrenia, including hyperlocomotion and ataxia. This observation is consistent with findings obtained in humans supporting the hypothesis that pathological (abnormal increased synchronization in) gamma oscillations are correlated with psychotic symptoms. / Schizophrenia-like psychosis of epilepsy (interictal psychosis) occurs in 3%–7% of patients with epilepsy including those with generalized non-convulsive absence epilepsy. Patients with generalised epilepsy have been reported to have an increased the power of their gamma frequency activity on the EEG. Ketamine and MK-801 also dose-dependently suppress SWD and concomitantly induces hyperlocomotion in WAG/Rij rats, genetic rat model of absence epilepsy. Thus, the study also investigated gamma oscillations in Genetic Absence Epilepsy Rats from Strasbourg (GAERS), and the effect of NMDA receptor antagonists. / METHODS: The relationship between quantitative measures of gamma power and locomotion was assessed in 8 freely moving rats following single injections of ketamine (<5 mg/kg) or MK-801 (<0.16 mg/kg). The impact of these NMDAr antagonists on neocortical gamma oscillations was also investigated in 24 anesthetized rats, including control experiments with substances that modulate dopaminergic neurotransmission. The second part of this study investigated the relationship between the spontaneously occurring gamma oscillations in the electrocorticogram of the neocortex and the quantitative measures of locomotor activity in eight freely moving non-epileptic control (NEC) rats and seven Genetic Absence Epilepsy Rats from Strasbourg (GAERS) before and after subcutaneous administration of a single dose of ketamine (<5.0 mg/kg), MK-801 (<0.16 mg/kg) or vehicle (sodium chloride, .9%). / RESULTS: NMDAr antagonists, ketamine and MK-801 were found to both induce highly correlated dose dependant hyperlocomotion and aberrant gamma oscillations, with the time course of this more prolonged in following MK-801. Ketamine and MK-801 also induced significant increase in the gamma power in deep urethane anaesthetized and neuroleptanagesized rats, and slight increase in the gamma power in pentobarbital anaesthetized rats. In the second part of the study the power of spontaneously occurring electroencephalic gamma frequency oscillations were demonstrated to be significantly increased (twofold) in GAERS compared to their non-epileptic counterparts (NEC). At the onset of the epileptiform spike-and-wave discharges (seizures) there was a dramatic increase (seven to nine fold) compared to interictal gamma power. The administration of the NMDAr antagonists induced dose-dependent highly correlated aberrant interictal gamma oscillations and hyperlocomotion in GAERS similar to that seen in the non-epileptic rates except that peak and total locomotor responses were siginificantely decreased in GAERS following ketamine administration and that GAERS had a later peak in gamma power and in hyperlocomotion compared to NEC rats following MK-801 administration. / CONCLUSIONS: The present study demonstrated that ketamine and MK-801 dose-dependently induced highly correlated hyperlocomotion and aberrant gamma oscillations in non-epileptic control rats, suggesting that abnormal increased synchronization in ongoing gamma oscillations in cortical-related networks might cause dysfunctions of conscious integration, as seen in patients with schizophrenia. The study also demonstrated that ketamine- and MK-801-induced gamma hyperactivity is not caused by ataxic behavior and hyperlocomotion and is independent on conscious sensorimotor processing. Ketamine and MK-801 also induced similar changes in gamma power in rats with geneticly epileptic rats (GAERS), however this occurred of a baseline of approximately double the gamma power of the non-epileptic rats. This later finding suggests that gamma suggests that frequency oscillations might have a role in process of epileptogenesis. Overall the study results support the exciting possibility that aberrant gamma oscillations are a promising potential endophenotype for schizophrenia and epilepsy that could be used in the development of novel therapies for these two complex brain disorders.

Thesis (M.D.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 185-230).

Thesis (M.S.)--University of Wisconsin--Madison, 1970. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (doctoral)--Bern, 1969. / "Sonderabdruck aus der Zeitschrift "European Neurology" Band 3, S. 168 1970."

Thèse--Universit́e de Lille. / "Index bibliographique": p. [91]-92.

Thesis (M.S.)--University of Wisconsin--Madison, 1966. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.