Cost minimization analysis of antiepileptic drugs in newly diagnosed epilepsy in 12 European countries.

A recent United Kingdom cost minimization analysis (CMA) of four antiepileptic drugs (AEDs) used to treat newly diagnosed adult epilepsy demonstrated that a new drug, lamotrigine (LTG), incurred higher costs than carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA), whose costs were similar. This analysis took account of each drug's side-effect and tolerability profile. The present analysis investigated the costs of treatment with LTG, CBZ, PHT, and VPA in 12 European countries. Data were derived from published sources and from a panel of locally based experts. When no published data were available, estimates were obtained using expert opinion by a consensus method. These data were incorporated into a treatment pathway model, which considered the treatment of patients during the first 12 months after diagnosis. The primary outcome considered was seizure freedom. Randomized controlled trials demonstrate that the drugs considered are equally effective in terms of their ability to achieve seizure freedom, and thus the most appropriate form of economic evaluation is a CMA. These trials provided data on the incidence of side effects, dosages, and retention rates. The economic perspective taken was that of society as a whole and the analysis was calculated on an "intent-to-treat" basis. Only direct medical costs were considered. In each country considered, LTG was twofold to threefold more expensive than the other drugs considered. A sensitivity analysis demonstrated that varying each of the assumptions (range defined by expert panels) did not significantly alter the results obtained.

Effect of vigabatrin addition on carbamazepine blood serum levels in patients with epilepsy.

Because vigabatrin (VGB) is not metabolized by liver enzymes and does not bind with serum proteins, there is little theoretical chance of it interacting with other antiepileptic drugs. However, our observations have shown that if VGB is added to carbamazepine (CBZ) monotherapy, some patients respond with adverse, toxic symptoms suggesting possible carbamazepine-vigabatrin interaction. This article presents the results of a study of 66 epileptic patients (27 women and 39 men), age 10-66 years (mean, 28.2 years), with focal seizure onset with or without secondary generalization. In these patients, in addition to CBZ therapy with an average dose of 16.7 mg/kg per day (8.6-26.8), VGB, average dose 31.1 mg/kg per day (7.1-57.9), was added. CBZ concentration was measured twice: prior to VGB introduction and 5-12 weeks after the final dose of VGB was reached. In our study 69.7% of patients responded to VGB addition with a significant increase (by at least 10%) in CBZ concentration. A correlation between the value of the increase and the initial level of CBZ prior to VGB addition was found also. Correlational analysis (Pearson's r) revealed a negative correlation between CBZ concentration and increased concentration after VGB addition (r = -0.47, df = 64, P < 0.001). This negative correlation means that if the initial CBZ level is lower, its concentration value after VGB addition is higher.

Posttraumatic epilepsy risk factors: one-year prospective study after head injury.

PURPOSE: Prospective evaluation of risk factors for posttraumatic epilepsy (PTE) by using clinical, EEG, and brain computed tomography (CT) data in four assessments from the head injury (HI) acute phase to 1 year later; and evaluation of the possible epileptogenic role of hemosiderin as shown by brain magnetic resonance imaging (MRI). METHODS: Risk factors for PTE were evaluated by using Kaplan-Meier curves, log-rank test, and the Cox model in 137 consecutively enrolled adult inpatients. Percentage differences of patients with brain hyperintense and/or hemosiderin areas shown by MRI 1 year after HI were statistically evaluated by univariate tests considering two subgroups [e.g., patients with (PTE) and without (WLS) late seizures]. RESULTS: The PTE subgroup included 18 patients with at least two seizures between the second and twelfth months. Kaplan-Meier curves demonstrated that Glasgow Coma Scale low score, early seizures, and single brain CT lesions are PTE risk factors, as is the development of an EEG focus 1 month after HI. No significant percentage difference was found between PTE and WLS patients with hemosiderin spots shown by MRI 1 year after HI. CONCLUSIONS: the Cox model indicates that, for HI patients with early seizures and brain CT single temporal or frontal lesions in the acute phase, the PTE risk is 8.58 and 3.43 times higher, respectively, than for those without. An EEG focus 1 month after HI is a risk factor 3.49 times higher than for patients without such EEG changes. One year after HI, a higher percentage of PTE than WLS patients had cortical MRI hyper-intense areas including hemosiderin.

Psychological approach of non-epileptic to epileptic patients: the dynamics of attitude changes during hospitalization.

Measures of interpersonal relations of non-epileptic patients to epileptic patients were studied in search of answers to two questions: what is the initial attitude of non-epileptic patients to epileptic patients; and, do any changes in attitude occur during time spent together in hospital? In order to study these personal relations, a formal analysis of preferences was carried out. Twenty-two non-epileptic patients admitted to the Neurology and Epileptology Department, Medical Centre for Postgraduate Education, Warsaw were studied. Subjects were asked to rank-order (from 1 to 9 points) suggested ways of distributing the profits of a hypothetical joint (e.g., with a room-mate) money-earning venture. The experimental procedure for each patient was repeated for all three room-mates. Preferences were assessed three times - the day after admission to hospital, after 11 days and after 21 days in hospital. Following this procedure, it was possible to trace the dynamics of the patients' interpersonal relations. The data were correlated (Spearman's r(s)) and submitted to analysis of variance (MANOVA) with repeated measures. Analysis of the attitudes of patients with non-epileptic neurological disorders towards epileptic patients revealed a dynamic tendency - from negative (measures one and partly two) to positive attitudes after three weeks spent together in hospital (measure three).

Psychogenic pseudoepileptic seizures: clinical and electroencephalogram (EEG) video-tape recordings.

This paper presents a clinical and electrophysiological analysis of type and duration of seizures recorded by means of long-term video electroencephalogram (EEG) monitoring, a method which enables accurate diagnosis of psychogenic pseudoepileptic seizures occurring with or without epileptic seizures. Analysis is based on 1083 patients, hospitalized at our department between 1990 and 1997, with a preliminary diagnosis of epilepsy. Psychogenic pseudoepileptic seizures were diagnosed in 85 patients (7.8%). In 48 patients, pseudoepileptic seizures alone were diagnosed (group 1), whereas 37 patients had a mixed condition in which pseudoepileptic seizures were accompanied by epileptic seizures (group 2). For comparison of duration of pseudo- and epileptic seizures a control group (group 3), consisting of 55 patients randomly selected from the population of patients suffering from epileptic seizures alone, was parceled out. Long-term video EEG monitoring was performed in 70 patients. In 55 (79%) of these patients 230 seizures (221 pseudoepileptic and nine epileptic) were recorded. In 30 patients (32%), the diagnosis was based on clinical observation of the seizures and on the number of EEG recordings, including activating procedures such as sleep deprivation, photostimulation, hyperventilation and anti-epileptic drug withdrawal. We found that the duration of epileptic seizures was significantly shorter than the duration of psychogenic pseudoepileptic seizures. Our study has exposed the difficulties involved in the diagnosis of psychogenic pseudoepileptic seizures and the negligible value of neuroimaging techniques and interictal EEG recordings in the differential diagnosis of epileptic versus nonepileptic seizures. In this study, psychogenic seizures were significantly more frequent in women than in men; patient history analysis did not confirm the hypothesis that sexual abuse may cause psychogenic seizures.

Prevalence of high IgM anticardiolipins in patients with ischemic stroke.

Lupus anticoagulant (LA), IgG and IgM isotypes of anticardiolipins (aCL), lipoprotein (a), and the resistance to activated protein C were determined in patients with ischemic stroke. The raised concentration of the aCL-IgM isotype was noted in 42% of patients with this type of stroke, and it was in contrast with an 8% frequency of an increased level of aCL-IgG isotype in these cases. The high level of lipoprotein (a) was found with similar frequency in stroke patients and in age-matched control subjects. It is concluded that the elevated concentration of IgM isotype of anticardiolipin antibodies can be regarded as significant in the ethiological work-up in elderly stroke patients.Copyright Lippincott-Raven Publishers

Strategies for rapid response to emerging foodborne microbial hazards.

The foodborne outbreak paradigm has shifted. In the past, an outbreak affected a small local population, had a high attack rate, and involved locally prepared food products with limited distribution. Now outbreaks involve larger populations and may be multistate and even international; in many the pathogenic organism has a low infective dose and sometimes is never isolated from the food product. Delay in identifying the causative agent can allow the outbreak to spread, increasing the number of cases. Emergency intervention should be aimed at controlling the outbreak, stopping exposure, and perhaps more importantly, preventing future outbreaks. Using epidemiologic data and investigative techniques may be the answer. Even with clear statistical associations to a contaminated food, one must ensure that the implicated organism could logically and biologically have been responsible for the outbreak.

A new route of transmission for Escherichia coli: infection from dry fermented salami.

OBJECTIVES: This study evaluated the production of dry fermented salami associated with an outbreak of Escherichia coli O157.H7 infection in Washington State and California. METHODS: Facility inspections, review of plant monitoring data, food handler interviews, and microbiological testing of salami products were conducted. RESULTS: Production methods complied with federal requirements and industry-developed good manufacturing practices. No evidence suggested that postprocessing contamination occurred. Calculations suggested that the infectious dose was smaller than 50 E. coli O157:H7 bacteria. CONCLUSIONS: Dry fermented salami can serve as a vehicle of transmission for O157:H7 strains. Our investigation and prior laboratory studies suggest that E. coli O157:H7 can survive currently accepted processing methods.

[A case of juvenile embryonal germ cell tumor of the mediastinum]. / Przypadek raka zarodkowego typu dzieciecego w sródpiersiu.

A rare case of a embryonal germ cell tumor of the mediastinum is presented in a 22 year old male. A radical excision of the tumor was performed, followed by chemotherapy. A five year survival was observed without evidence of a recurrence.

Carbamazepine effects on afterdischarge, memory retrieval, and conditioned avoidance response latency in hippocampally kindled cats.

Carbamazepine (CBZ) effects on (a) complex partial seizures and afterdischarges (AD), (b) memory retrieval, and (c) conditioned avoidance response (CAR) latencies were studied in a group of 9 hippocampally kindled cats. Significant AD and epileptic seizure suppression was observed in kindled cats after administration of CBZ concurrent with significant improvement in percentage scores on the memory retrieval test. The CAR latencies were longer in kindled cats with or without CBZ than in the conditioned group of cats without both kindling and CBZ. CAR latencies were not significantly different between kindled and kindled-CBZ-treated cats. Thus, the longer latencies in kindled animals cannot be due to CBZ but apparently are related to the effects of kindling. In some kindled animals, longer CAR latencies were reversed by CBZ.

[Pathogenesis of epileptic focus]. / Patogeneza ogniska padaczkowegó.

An epileptogenesis as well as relation between epileptogenesis and memory consolidation have been analysed with kindling model. A role of kindling in pathogenesis of seizures in man, including formation of the secondary epileptic foci, has been discussed. An emphasis is on a controversial significance of gliomatous scar for the formation of epileptic focus and spreading of discharges on the adjacent brain structures.

EEG afterdischarge patterns and performance of the avoidance response in hippocampally kindled cats.

The relation between EEG limbic afterdischarge patterns and the performance of avoidance response was studied in eight hippocampally kindled cats. Five basic types of EEG afterdischarge patterns were identified in the hippocampal formation: (i) continuous 2-4/s high amplitude spikes or spike and wave complexes; (ii) continuous, 4.5-12/s high amplitude spikes or spike and wave complexes; (iii) dysrhythmic pattern: disorganized irregular spiking, mixed with slow waves at 3-20/s frequency; (iv) continuous, 20-30/s comb-like shaped spiking of moderate amplitude, and (v) trains of high amplitude and frequency irregular spikes, lasting for 0.2-1 s. followed by EEG depression lasting 0.3-1 s. The performance of conditioned response was tested during first 10 s. of afterdischarge development after kindling electrical stimulation of the hippocampus. A statistically significant relation was observed between the EEG afterdischarge patterns seen at the beginning of afterdischarge formation (basically types I, II and III) and the performance of avoidance response, with greatest probability of the response failure with type III of afterdischarge pattern. Latencies of the avoidance responses were prolonged during afterdischarges, in comparison to latencies observed before and after kindling hippocampal stimulation.

Effect of after-discharge EEG patterns on performance and latency of the conditioned avoidance response in hippocampally kindled cats.

The relation between different EEG after-discharge patterns and memory retrieval of the conditioned avoidance response was studied in 8 hippocampally kindled cats. The after-discharge patterns were classified into 5 basic EEG types. The relation was analyzed in three different situations: A, at the conditioning stimulation onset, B, at the conditioning stimulus termination, and C, when conditioning stimulus onset and termination were studied within the same type of EEG pattern of after-discharge. The moment of presentation of the conditioning stimulus was determined by the type of EEG after-discharge pattern. Significant relation was observed between reflex performance and type II and III EEG AD types. The type II (4.5-12/s spiking activity) was associated with a greater proportion of positive responses if presented on the uniform background of EEG after-discharge patterns. During the type III pattern (EEG dysrhythmia), there were more negative than positive responses in all the three experimental situations, especially if the type III EEG pattern was observed at the time of conditioned stimulus termination. The latency of reflex performance measured in the experimental condition C (the same pattern of EEG during conditioning stimulus onset and termination) was longer during the type II EEG pattern of after-discharges than the latencies found during type III EEG activity and in the control group. During type III pattern associated with greatest proportion of response failures there was, however, no increase of reflex latencies. The results suggest differential effect of different EEG after-discharge patterns on memory retrieval of the well established conditioned avoidance response in cats.

Influence of hippocampal kindling on avoidance learning in cats.

The formation of avoidance response and differentiation was studied in 13 control and 7 kindled cats with developed hippocampal epileptic focus and complex partial or secondary generalized tonic-clonic seizures. Conditioning sessions lasted from 15 to 20 min in a period following afterdischarges and seizures resulting from electrical stimulation of the hippocampal formation. In two out of seven kindled cats the conditioned reflex was established within time limits (9 and 20 days) comparable to the control cats. These two animals had relatively short-lasting afterdischarges (mean values: 17 and 19 s). In cats with longer-lasting afterdischarges and complex partial seizures (mean duration: 32 to 65 s, in different animals) criterion was not reached during parallel kindling-conditioning stage of 10 to 30 days. The level of correct responses was low and variable (0-70 percent), despite typical reactions to the unconditioned stimuli and clear orienting responses to the conditioning stimuli on more advanced stages of training. Four kindled animals entered the stage of secondary generalization of seizures after hippocampal stimulation. Reflex performance after tonic-clonic seizures was practically abolished. The termination of kindling resulted in acquisition of the conditioned reflex in all the animals. The results indicate, that in animals with long-lasting complex partial seizures the learning of the avoidance response is impaired. In contrast to the effects exerted by afterdischarges and complex partial seizures, intensive interictal hippocampal spiking did not seem to have a direct negative influence on, this particular type of learning.