Quality of life of patients with epilepsy (Hungarian survey).

We assessed the quality of life (QOL) of patients with epilepsy using the Quality of Life in Epilepsy Inventory (QOLIE-31). As the first step we compared our results with the data from an American survey in order to validate the test in Hungary. The results show that the Hungarian values were lower but that they followed the same trends as the American data. There was only one controversial result in the question-group of the 'the effects of treatment', which could be explained by the differences in habits and conventions, opportunities and expectations between Hungarian and American epileptic patients. We found significant differences in many aspects of quality of life with respect to (a) gender (general quality of life, seizure worry), (b) pharmacological treatment form (cognitive functions, medication effects, total score and social and role functioning) and (c) economic activity of patients (cognitive functions, emotional well-being, energy/fatigue, medication effects, overall quality of life, overall scores, seizure worry, social and role functioning). We have tried to explain the differences found by taking either the characteristics of epilepsy or the social background of the epileptic patient into consideration. Based on previous knowledge we have tried to define the situations where the assessment of quality of life for people with epilepsy, may be beneficial to their core.

Hungarian multicentre epidemiologic study of the warning and initial symptoms (prodrome, aura) of epileptic seizures.

We carried out a Hungarian multicentre study to assess the frequency of the occurrence of warning symptoms preceding epileptic seizure. The data of 562 patients with epilepsy out of a total of 1124 were analysed on the basis of questionnaires filled in under standard conditions. About 50% of the patients experienced warning symptoms before a smaller or greater part of their seizures. Their appearance was fairly consistent and became mainly manifested in the form of headache, epigastric sensation and dysphoria. In relation to epileptological basic data, it was found that warning symptoms appeared primarily in focal epilepsies and among them they mainly preceded generalized tonic clonic and complex partial seizures. Between the warning symptom and the onset of the seizure there was usually a longer interval during which (and generally also during the warning symptom) the patient remained able to act. About 20% of the patients enrolled in the study tried to inhibit the onset or mitigate the course of the seizure and about 10% judged their spontaneous activity carried out in that direction to be successful. The frequency of the occurrence of independent prognostic symptoms not followed by a seizure was relatively low, and among epileptics with warning symptoms the incidence of seizures occurring without a preceding event was not high either. Based on our experiences, we have drawn the conclusion that, in a significant part of epileptic patients, the warning symptoms render possible the supplementation of the therapy by the development of seizure-inhibiting or seizure-avoiding behaviour or activity.

A theoretical approach to the contribution and significance of physiological antiepileptic systems in the clinical manifestations of epileptic symptoms.

The onset an of epileptic seizure is the most striking event in the pathophysiology of epilepsy from the clinical aspect. Present knowledge concerning the pathomechanism of the disease does not explain why, in spite of a permanent epileptic dysfunction, the occurrence of clinical seizures is relatively rare even in severe epilepsies. According to my hypothesis, the clinical picture is determined by the balance of two systems of opposite nature (i.e. epileptogenic and antiepileptic). Regarding these systems, research has focused exclusively on the former. A short survey is given here of everyday clinical and EEG experiences which cannot be explained on the basis of epileptic dysfunction and may therefore be considered as indirect evidence of the existence of a physiological antiepileptic system. The hypothesis may also help to explain some special events like occasional epileptic symptoms, 'positive' electroencephalography without clinical signs and the influence of provoking factors. It further clearly shows the place of nonpharmacological (psychological) treatments for epilepsy, stressing the importance of an holistic attitude.

Task related difference EEG spectrum--a new diagnostic method for neuropsychiatric disorders.

ERDS is a new method that was developed to detect EEG changes during a short mental task (reverse counting). It is recommended for testing cognitive EEG in organic mental disorders. The essence of the task situation is that it needs continuous mental work during a short period of time. The level of task difficulty must be adapted to each patient's actual mental capacity. To preserve continuity of the mental work, the level of difficulty might be changed instantly by the EEG technician in case of a longer break or multiple mistakes by the subject in the task. For analysis, artifact-free EEG sections are manually selected. Differences of pre-task and post-task EEG power spectra (ERDS) and differences of the peak and mean frequencies are calculated. Based on our initial experience on 100 ERDS tests, this method demonstrates cognitive EEG changes related to the task. Each patient's pre-task EEG serves as control data that is compared to post-task changes. Hence, confounding effects on the ERDS test are minimal, i.e., the effect of individual EEG features or those EEG signs of the disease or therapy that are independent of cognitive functions. Therefore, ERDS test results can be considered as markers of cognitive state in diverse pathological conditions. They also enable us to follow changes during the spontaneous course of mental illness or due to therapeutic interventions. Appropriate instruction of patients about the task, attention of the technician in order to preserve the patient's continuous mental work, and to insure patient compliance are very important. Further investigation is necessary for validation of the method and to build a database of tests on healthy population of different age groups and of patients with different psychiatric conditions. Standardization of the test is essential for the introduction of ERDS to the every-day routine of clinical neuropsychiatry.

Assessing the sedative (adverse) effects of antiallergic drugs by quantitative electroencephalography: effects of setastine a non-sedating antihistaminic drug.

In order to assess the effects of Loderix (setastine) on the EEG ten healthy male volunteers were investigated in double-blind, placebo-controlled, cross-over arrangement. In addition to the test compound (Loderix) volunteers were treated with vehicle and with two referent drugs (terfenadine, Teldane, and chloropyramine HCl, Suprastin) possessing sedative effects of very different degrees. The different effects of the referent drugs on the central nervous system (CNS) were precisely indicated by the posterior alpha/theta ratio in the EEG. This marker parameter was affected by Loderix in the same direction as by Teldane and in the opposite direction as compared to Suprastin. In addition, Loderix increased the beta frequency range in the median areas of both hemispheres, moreover, it increased the total EEG power. The latter changes raise the question if Loderix has an "own" action on the EEG. (The observed "own" effect could not even be brought into connection with decrease of the vigilance level). The results strengthen the view that the action of Loderix on the EEG is similar to that of induced by Teldane, a drug very favourable in respect of the sedative side effects. Moreover, the drug did not affect the EEG power spectra in a direction that referred to sedative action. The spectral parameters in the "pharmaco" EEG recordings seem to be useful in the objective definition of the central (psychotropic) side-effects of drugs. This is a methodical achievement of the present study.

Correlations between night sleep duration and seizure frequency in temporal lobe epilepsy.

Correlations between occurrence of complex partial seizures and altered sleep duration were analyzed in a small but strongly homogeneous population of temporal lobe epilepsy patients. Sleep deprivation and oversleep were determined individually; 682 epileptic seizures occurring on 4,995 days were related to occasional alterations of night sleep duration. The seizure-inducing effect of an actual relative sleep deprivation was 67-100% in four cases and 49-64% in four cases. Oversleep had no consistent seizure-provoking effect. Relative sleep deprivation may have a seizure-provoking effect, especially in temporal lobe epilepsy. This information may be used to instruct epileptic patients concerning sleep hygiene which might improve the efficacy of antiepileptic drug (AED) treatment, even if no change is made in medication.

Sensory stimulation for inhibition of epileptic seizures.

Simple acoustic stimuli were delivered at the onset of absence seizures in 23 investigations of 19 patients. In 79 of 139 observations, the stimulation promptly inhibited the seizure. The most effective inhibition was achieved in the first 3 s of the absence seizure. An automatic system of self-stimulation is recommended for further investigations. Following solution of some theoretical questions and technical problems, the suggested method can become a new therapeutic modality in seizure treatment.

Life events and seizure frequency in epileptics: a follow-up study.

On the basis of 2227 examinations of 272 epileptic patients the connection between the seizure frequency and life events of negative or positive emotional nature was analysed. Negative life events went with a deterioration, positive factors with a decrease of seizure frequency in most cases. Results of antiepileptic serum measurements suggest that emotional factors exert their effect by influencing the patient's compliance. Supposed intrapsychic patho-mechanisms of this connection are briefly discussed. Authors' results stress the importance of psychic care of epileptics simultaneously with medical treatment.

Place of phenytoin in treatment of resistant epilepsy.

A retrospective therapeutical follow-up of 64 therapy-resistant epileptics treated by phenitoin (DPH) is made chronically. In the study 232 treatment periods of at least two years' duration were analyzed. Distribution of DPH therapeutic combinations was evaluated according to the type of epilepsy, seizure form, seizure frequency, elements of patient compliance, and results of serum level measurements. According to the author's opinions DPH is still one of the most effective agents in the treatment of resistant epilepsy, but in most cases as a constant component of antiepileptic bitherapy. Its pharmacokinetic features and optimal dosage show great individual variability, larger than that of other drugs and, in cases of combined drug regimens, interactions may more frequently be expected.

K-complex formation of the EEG in sleep. A survey and new examinations.

The first part of the work offers a survey of the literature on the K complex. In the second part the authors' own investigations are discussed. The data come from three series of experiments: 1) from five sleeps of eight subjects (s) observed under different experimental conditions: 2) from twenty-one nights spent without stimulation and fourteen nights at acoustic stimulation of the same s; 3) from the analysis of the K complexes appearing in stimulated and non-stimulated periods alternating every five minutes of stages 2 in the first cycles of 6 sleeps of another s. In five sleeps of an identical s the K complexes were examined also by means of averaging. The frequency of the K complexes was greater in the stages 2 ascending type than in those of descending type. Sensory stimulation increased the formation of K complexes in the ascending slopes of the cycles to a higher degree than in the descending ones. Repression of the K complexes appearing on the effect of stimulation in the ascending slope was more marked than in the descending one. These findings indicate a close connection of the formation of K complexes and phasic sensory activation. At the same time a connection between K-complex formation and the measure of sleep synchronization was observed. From evening to morning the frequency of K complexes decreased from cycle to cycle, parallel with the decrease in the depth of sleep. Similarly, the frequency of the K complexes measured in stages 2 showed a relationship with the depth of the cycles: the deeper the sleep in the given cycle, the more the K complexes found in unit time in stages 2 belonging to the cycle anchoring the measured stage 2. The EEG responses that could be identified with K complexes elicited by means of acoustic stimuli could be demonstrated by averaging in the whole slow-wave sleep. It is assumed that the EEG phenomena of K complex-type of spontaneous sleep arise under the effect of continuous sensory activation, hence they correspond with nonspecific evoked potential elements, and therefore the K complex can be regarded as a building stone of slow-wave sleep. At the same time K complexes were interpreted as conflict products of sensory activation and sleep-protecting influences and considered important indicators of the dynamics of the sleep-waking system.

Pharmaco-EEG profiles of antidepressants. Pharmacodynamic studies with fluvoxamine.

1 Antidepressant drugs produce significant changes in human brain function as reflected in the quantitatively analysed EEG. Two main types of pharmaco-EEG profiles may be differentiated: a thymeretic (desipramine-like) profile characterised mainly by an alpha increase suggesting activating properties and a thymoleptic (imipramine- or amitriptyline-like) profile showing a concomitant increase of slow and fast activities and a decrease in alpha activity indicating also sedative qualities. A small number of compounds exhibit still different profiles. 2 Aside from determining the type of EEG changes, the pharmaco-EEG method seems to be of value in determining time and dose efficacy relations at the target organ, the human brain. Moreover, the relationships between pharmacodynamics and pharmacokinetics may be determined. 3 Fluvoxamine, a selective 5-hydroxytryptamine (5-HT) re-uptake inhibitor from the new class of 2-aminoethyloximethers of aralkylketones, produced a typical thymoleptic pharmaco-EEG profile after oral doses of 75 mg in a double-blind placebo-controlled study involving 10 healthy volunteers. Fluvoxamine (75 mg) induced less augmentation of slow activity than 75 mg imipramine, indicating less sedative properties of fluvoxamine than imipramine. 4 After 75 mg fluvoxamine psychometric tests demonstrated a tendency towards an improvement in attention, concentration, psychomotor activity, after-effect and mood and a significant increase in critical flicker fusion frequency as compared with placebo. Comparison with the reference drug, 75 mg imipramine, revealed a significant superiority of fluvoxamine regarding concentration, psychomotor activity, tapping, reaction time, mood and affectivity. 5 Side-effects (mostly tiredness) were seen in five out of 10 subjects after 75 mg fluvoxamine and in eight out of 10 subjects after 75 mg imipramine. There were no clinically relevant changes in pulse, systolic and diastolic blood pressure.

Vigilance level-dependent tonic seizures--epilepsy or sleep disorder? A case report.

A case with vigilance level-dependent, nightly occurring, generalized, axial, tonic motor seizures without any ictal or interictal scalp electroencephalographic expression is presented. A pathological sleep pattern with many arousals, superficial sleep, and an interrelation between the seizures and the arousal episodes was demonstrated. An epileptic excitation discharge during the seizures was verified on the right cingular cortex by stereoencephalography. The physiopathogenesis and differential diagnostic problems in the interpretation of such cases as a sleep disorder or an epileptic mechanism are discussed.

Clovoxamine and fluvoxamine-2 biogenic amine re-uptake inhibiting antidepressants: quantitative EEG, psychometric and pharmacokinetic studies in man.

In a double-blind placebo-controlled study, the encephalotropic, psychotropic, pharmacodynamic and pharmacokinetic properties of 2 new substances, clovoxamine (a 5-HT and NE re-uptake inhibitor) and fluvoxamine (a selective 5-HT inhibitor) were investigated utilizing quantitative pharmaco-EEG, psychometric and blood level analyses. Ten normal volunteers received randomized and in weekly intervals oral single doses 50 mg, 75 mg and 125 mg clovoxamine, 75 mg fluvoxamine, placebo and as reference drug 75 mg imipramine. Quantitative EEG, psychometric data, pulse, blood pressure, side effects and pharmacokinetic data were studied at the hours 0, 2, 4, 6 and 8. Plasma levels of both substances peaked in the 4th to 6th hour and declined slowly thereafter. Digital computer period analysis of the EEG demonstrated after clovoxamine only minor changes characterized by an increase of fast beta-activities suggesting slight activating qualities of the drug. On the other hand 75 mg fluvoxamine and especially 75 mg imipramine produced marked CNS changes characterized by a concomitant increase of slow and fast activities and a decrease of alpha-activity. However, 75 mg fluvoxamine induced less augmentation of slow activity than imipramine indicating less sedative properties of fluvoxamine than the standard reference drug. Psychometric tests demonstrated after 50 and 75 mg clovoxamine and 75 mg fluvoxamine an increase in attention, attention variability, concentration, CFF and after-effect in the Archimedean Spiral (indicating central activation), further an improvement in mood and affectivity as compared with placebo, while 125 mg clovoxamine and 75 mg imipramine produced an increase in reaction time, deterioration of mood and affect and psychomotor activity. The latter changes were observed also after other antidepressants in normals. Pharmacodynamic investigations regarding dose-efficacy and time-efficacy relations based on both EEG and psychometric parameters revealed that 75 mg imipramine was the most effective compound, followed by 75 mg fluvoxamine and 125 mg, 75 mg and 50 mg clovoxamine. The peak effect of clovoxamine and fluvoxamine was observed around the 6th hour, while 75 mg imipramine was maximally observed around the 6th hour, while 75 mg imipramine was maximally effective between the 2nd and the 4th hours. Side effects were minimal after clovoxamine (interestingly euphoria in 3 subjects), while tiredness was seen in 5 out of 10 subjects after 75 mg fluvoxamine and in 8 out of 10 subjects after 75 mg imipramine. There were no clinically relevant changes in pulse, systolic and diastolic blood pressure.

Impact of maternal education and health services on child mortality in Uttar Pradesh, India.

"This article, which examines the effect of maternal education on child mortality [in India], shows that education has direct as well as indirect effects through antenatal care and family formation patterns on neonatal mortality. Maternal education also has a substantial effect on later childhood mortality. While improving maternal education is a means of reducing childhood mortality, an immediate reduction in childhood mortality is feasible even under existing social conditions by enhancing accessibility to maternal and child health services and safe drinking water."

Event-related non-specific responses (K-complexes) during sleep.

EEG responses to sensory stimuli were obtained by averaging. In averages representing the reactivity of the approx. 5 min sleep period, the fluctuation of the amplitude of the obligatory part was evaluated. The deepening of sleep was reliably indicated by the increase in amplitude while the lightening of sleep by a decrease in amplitude within stage 2. In longer sleep periods beside the above tendency a micro-fluctuation occurred as evidence of the fine fluctuations of the sleep level within the phases. The synchronization response could be followed by this method even in the deep sleep stages and the above behaviour of the amplitudes of averages remained unchanged. This shows that the synchronization response to arousal stimuli is a uniform phenomenon during the whole slow-wave sleep. Our results support the assumption that the spontaneous or evoked synchronization phenomena in sleep are the products of the dynamic balance in the sleep-arousal system. An increase of amplitude may indicate an increase in the tonus of the sleep system while its decrease an opposite process. The present observations, similarly to our earlier results, may be adapted well to the sleep model based on the phasic activation and reciprocal induction theory.

Micro-arousals during nocturnal sleep.

In 8 young adult human subjects EEG- and polygraphic characteristics of transient shifts towards arousal (micro-arousal, MA) have been studied during sleep under five different experimental conditions in 40 night sessions. Out of the five applied experimental situations, two (psychostimulant application and sensory stimulation) resulted in a shift of the balance between the systems of sleep and arousal towards an increased activity of the arousal system, while an other condition (rebound following partial sleep deprivation) led to an opposite change to a rise in "sleep pressure". An inverse correlation has been found between the frequency of MA and the depth of sleep, a finding consistently observed in every subject and in every experimental situation. During the process of sleep periodic changes in the dispersity of MA could be seen; the number of MA-s decreased and increased according to the descending and ascending slope of the sleep cycles. During the ascending slope of cycles there was a coupling between the occurence of MA-s and the changes of phases. Increases in the level of activation and in sleep pressure did not influence the occurrence of MA-s. Increasing the tone of the arousal system in chemical way, or by means of enhancing the phasic sensory input resulted in a reduction of the difference between the number of MA on the descending and ascending slopes of cycles. During the phases of sleep, the spontaneous occurrence of MA-s went parallel with the possibility to evoke MA-s by sensory stimuli. These data show that MA is a regular phenomenon of nocturnal sleep; MA manifests itself as a result of phasic functioning of the reticular arousal system and plays a role in the organization of those periods of the sleep cycle, which tend toward arousal. It is suggested that MA-phenomenon is considered a standard measure of sleep and that it could represent an indicator of the function of the arousal system controlled by external or internal mechanisms during sleep.