[Renin-secreting tumor detected by MRI]. / Tumeur à rénine découverte par IRM.

We report an uncommon case of small renin secreting tumor of the kidney located in the medulla. The tumor was primarily detected by MRI and subsequently studied by spiral CT. The results and limitations of both techniques are discussed.

[Electroencephalographic findings in dementia diseases]. / Elektroenzephalographische Befunde bei dementiellen Krankheitsbildern.

Even if generally the EEG cannot yield specific pointers that are typical for a special pattern of dementia, it is nevertheless meaningful and helpful to perform routine EEG in demented patients. EEG is the functional additional examination that does not place any stress on the patient and is easy to perform at a low cost (1). As a functional diagram the EEG reflects the electrical processes taking place in the cerebral cortex, yielding an excellent image of the cerebral functional state. Assessment of the EEG is done in accordance with internationally standardised criteria. Particular attention is directed at a slowing-down of the background activity, the occurrence and extent of scattered theta and delta waves, their topographical distribution and the development of pathological EEG characteristics during recording (44). Update spectral analysis EEG procedures, i.g. the possibility to calculate power spectra for the individual EEG frequency bands and their topographic distribution, it may be possible in the near future to further improve differentiation between normal and pathological EEG findings. The functional dynamic aspect of the EEG is its particularly strong point in the differential diagnostic clarification of dementia patterns. By repeated EEG recordings, i.e. by close follow-up, and by relating the electrophysiological findings to the clinical pattern, reliable pointers are obtained for the extent of the activity of the process underlying the dementia pattern. EEG is predestined like no other method to enable early detection of rapid changes in cerebral function thanks to its easy operation and unlimited repeatability. The occurrence of parenrhythmic theta and delta waves in the EEG reflects in a special manner the acuity of an organic basic process. In this way EEG enables differentiation between acute and chronic processes of cerebral damage. Over and above this, correlation with the relevant clinical findings makes it possible to differentiate between reversible states of dementia and irreversible defect syndromes and hence also to point to the long-term outcome. Finally, the occurrence of certain patterns of findings or the identification of characteristic wave forms allows essential differential diagnostic pointers and definitions.

[The course of pregnancy and teratogenicity of antiepileptic agents in 66 patients with epilepsy]. / Untersuchungen zum Schwangerschaftsverlauf und zur Teratogenität der Antiepileptika bei 66 Epilepsie-Patientinnen.

We report on 79 pregnancies in 66 female outpatients with epilepsy. An increase of seizure frequency was significantly more frequent in complex partial seizures than in grand mal seizures and in absences. The reason for these disparities are not clear. In most patients a raised frequency of seizures during pregnancy decreased again after delivery. Carbamazepine was the antiepileptic drug prescribed most frequently followed by valproic acid. The course of the blood levels of carbamazepine and valproic acid was nonuniform during pregnancy. Total concentrations of carbamazepine in cord blood were on average 84.5% of those in maternal blood (n = 22). Valproic acid blood levels were on average 183% of those in maternal blood (n = 15). It is still unclear whether these differences are clinically relevant. During the last weeks of pregnancy we found an increase of the free fraction of carbamazepine and valproic acid. Simultaneously the total protein concentration decreased. Until now these findings are without clinical relevance. The course of labor did not differ from normal population concerning the ratios of spontaneous labor, cesarean section and delivery by forceps. Miscarriage and perinatal mortality were 2.7% each and outnumbered the risk in the general population. In 42.8% of the neonates one to three perinatal complications were observed. The ratio of perinatal complications is not different between patients with monotherapy and combined therapy respectively. There was a tendency to lower values of length, weight and head circumference in the male neonates but not in the female neonates. The risk of minor malformations was 26%, the risk of major malformations was 14% (including one case of suspected malformation) without a discernible correlation with a specific antiepileptic drug.

[Epileptic psychoses and their drug treatment]. / Epilepsiepsychosen und ihre medikamentöse Behandlung.

This paper is concerned with classification, clinical-electroencephalographic correlation, principles of treatment, and pharmaceutic therapy of epileptic psychoses. Based on the system of the physically founded reversible psychoses, classification of epileptic psychoses is developed, which is easy to apply for clinical and research purposes. Its principles are the criteria of disturbance of consciousness and of connexion to epileptic seizures. Epileptic psychoses without disturbance of consciousness frequently go along with a forced normalization of epileptic EEG-changes. This clinical-electroencephalographic correlation is documented by the cases of a depressive-paranoid and a cenesthetic alternative-psychosis. Epileptic psychoses connected to seizures, going along with disturbances of consciousness, however, show, without any exception, a pathological changed EEG. Also in the cases of the often iatrogenically produced epileptic psychoses with disturbances of consciousness yet not connected to seizures, the EEG-results are of decisive diagnostic importance. Each of these three clinical-electroencephalographically defined groups of psychoses calls for concentration on particular pathogenetical aspects concerning a specific pharmaceutic therapy. The respective principles of treatment are developed in subtly differentiated ways and they are provided with suggestion as to medicamental treatment. Schizophrenia-like epileptic psychoses are a model for idiopathic schizophrenias and so important perspective opens up for research.

[HMPAO-SPECT in cerebral seizures]. / HMPAO-SPECT bei zerebralen Anfällen.

In nine patients with suspected psychogenic seizures and in three patients with proven epileptic seizures HMPAO-SPECT was performed prior to and during seizure. In the patients with later on-proven psychogenic seizures no, or only slight, changes of regional cerebral blood flow were found. Patients with proven epilepsy revealed partly normal findings interictally but during seizure a markedly increased circumscript blood flow was found in all patients. Even though PET is superior to SPECT with respect to spatial resolution, in the diagnosis of seizures HMPAO-SPECT has the advantage of enabling injection of the tracer during the seizure and the performance of the SPECT study subsequently.

Double-blind placebo-controlled trial with flunarizine in therapy-resistant epileptic patients.

The anticonvulsant efficacy and side-effect liability of flunarizine (15 mg/day) was investigated in a randomized, double-blind, placebo-controlled, crossover design in 30 outpatients with drug-resistant complex partial seizures. Flunarizine or placebo was added to the preexisting medication and each patient was followed up for 10 months. At the end of the study data from 22 patients were available for evaluation. In patients taking first flunarizine and then placebo, plasma levels of flunarizine were still detectable at the end of the 4 months' placebo phase. In the group of 13 patients starting therapy with placebo, a significant seizure frequency reduction was observed during the flunarizine period in 11 patients, whereas one patient showed no change and seizure frequency increased in another patient. Two patients had a 50% reduction in seizure frequency. Flunarizine was well tolerated and few side effects were noted.

Functional and morphological abnormalities in temporal lobe epilepsy: a comparison of interictal and ictal EEG, CT, MRI, SPECT and PET.

Ten patients suffering from drug-resistant complex partial seizures, with EEG abnormalities in the temporal region, were studied by means of non-invasive electrophysiological techniques (video-monitored, 16-channel, prolonged surface and sphenoidal EEG) as well as by imaging techniques (CT, MRI, SPECT and PET). Analysis of interictal and ictal EEG indicated the localization of epileptic activity in one side in eight cases. CT demonstrated focal abnormalities in three, SPECT in five unequivocally (in another four questionably, with the same lateralization as indicated by PET), MRI in eight, and PET in all cases. While only EEG provided specific diagnostic information, the focus definition was consistently good on PET images, poor on CT scans, and generally good but less consistent on MRI.

Epileptic activity during sleep and wakefulness.

In 23 untreated patients the temporal distribution of generalized spike-wave activity was investigated by means of mobile long-term EEG recordings. Distribution classes (S, A, W) were defined if the relative amount of epileptic activity within the phases sleep, awakening and waking exceeded a threshold, otherwise a diffuse distribution (D) was scored. A, S and D distributions were found approximately with the same frequency. In no patient was the middle part of the night most prominent. In one patient, it was shown by micro-hypnograms that 'micro-arousals' are closely related to spike-wave activity.

Studies on the intracerebral metabolism of anticonvulsant drugs--II. Disposition of carbamazepine in the isolated perfused rat brain.

Carbamazepine (CBZ) was perfused (85 nmoles/ml) through the isolated brains of rats. After 2 hr the mean regional concentrations of the drug were between 170 and 234 nmoles/g wet weight. The total brain content of CBZ was 390 nmoles. During perfusion 82 nmoles epoxycarbamazepine (E-CBZ) were formed, most of which were found in perfusion medium. Tissue levels of E-CBZ were between 0.3 and 2.8 nmoles/g wet weight. No dihydroxycarbamazepine (DH-CBZ) could be found. Pretreatment of the rats with phenobarbital neither influenced the uptake of CBZ into the brains nor increased the formation of E-CBZ significantly.

Free level monitoring of carbamazepine and valproic acid: clinical significance.

The recently available ultrafiltration technique facilitates determination of the free drug serum concentration of several antiepileptic drugs. For this reason a reappraisal of the clinical significance of free level monitoring was thought necessary. In this study on 203 patients receiving carbamazepine monotherapy and 101 patients receiving valproic acid monotherapy, the total and free drug levels were correlated with therapeutic outcome and side effects. Our investigations indicated no closer correlation between free concentration and seizure reduction or side effects than between total concentration and effectiveness or side effects. However, we found a close correlation between total and free concentrations.

[Cerebral emission computer tomography (SPECT) with 123I-labeled amphetamines]. / Zerebrale Emissions-Computertomographie (SPECT) mit 123J-markierten Amphetaminen.

Amphetamine is stored by brain tissue and permits its scintigraphic imaging, particularly with the single-photon emission computed tomography (SPECT). A total of 60 scintigraphic investigations in 54 patients were done. Investigations were done using an emission computed tomograph (rotating gamma-camera) after application of 123I-N-isopropyl-amphetamine. In 6 out of 24 patients with epilepsy a focus in agreement with EEG findings could be established despite negative cranial computed tomography (CT). In 4 out of 25 patients with cerebrovascular disease diminished perfusion was demonstrated although cranial CT was normal. In 10 out of 20 cases the extent of functional lesions demonstrated by SPECT was larger than could be assumed by cranial CT findings. Three patients with migraine and negative CT findings showed disorders of perfusion in the amphetamine-SPECT which were in agreement with the EEG. Brain SPECT using 123I-labelled amphetamines thus offers the possibility to demonstrate functional perfusion and metabolic disorders which show no morphologic correlate in the cranial CT. In addition, foci demonstrated in cranial CT can be more precisely defined in their functional extent using the SPECT.

Studies on the intracerebral metabolism of anticonvulsant drugs--I. Perfusion of primidone through the isolated brain of the rat.

Primidone and phenobarbital (each 85 nmoles/ml were separately perfused through the isolated brain of the rat. After 5 min of perfusion similar amounts of primidone and phenobarbital were taken up into the brain; for both drugs the concentration ratio between brain and perfusion medium was about 0.2. However, after 2 hr of perfusion the mean concentration ratio for primidone was about 0.55; for phenobarbital it was about 0.9 thus indicating a better uptake of phenobarbital. In two regions (hypophysis, mesencephalon) the concentration of phenobarbital was significantly higher than in perfusion medium. During 2 hr of perfusion of primidone, substantial quantities of phenobarbital and PEMA were formed amounting to 1400 pmoles for each metabolite. The highest concentration of the metabolites was found in septum, hypothalamus, hypophysis and mesencephalon. The in situ metabolism of primidone in the intact brain was demonstrated for the first time.

[The spread and inhibition of epileptic processes, findings with the kindling model in the cat]. / Aspekte der Ausbreitung und Hemmung epileptischer Prozesse, Befunde mit dem Kindling-Modell an der Katze.

The study was undertaken to describe some characteristics of subcortical brain activity during the development of an experimentally induced seizure disorder in the cat, as well as to test inhibitory effects of caudate counterstimulation. A further objective was to assess the use of closed circuit TV monitoring for the evaluation of clinical symptoms in an experimental model of limbic epilepsy. The analysis of event related potentials, spectral coherences and phases was especially suitable in order to detect a gradual lowering of the seizure threshold during the establishment of a unilateral Nucl. amygdalae epileptic focus. The results demonstrated evidence for the proceeding importance of hippocampal involvement during the development of seizure activity originating in the ipsilateral amygdala. No evidence, however, could be found for the existence of inhibitory functions triggered by stimulation of the ipsilateral caudate nucleus. The simultaneous split-screen TV monitoring of EEG and partial complex symptoms proved to be a valuable tool for the documentation of seizure patterns during the kindling procedure.

Intensive follow-up monitoring in patients with once daily evening administration of sodium valproate.

For 18 previously untreated patients with absence, myoclonic, or grand mal seizures--or combinations--results of clinical and electroencephalographical monitoring are reported. Sodium valproate was given once daily in the evening. Monitoring included repeated 24-48 h EEG recordings and drug blood level measurements. Results indicated the evening monodose to be an adequate therapeutic schedule for a considerable number of patients. Apart from the aspect of simplification, a further important aim is to individually minimize the drug dose. An average of 15.6 mg/kg sodium valproate (range, 10.0-25.5 mg/kg) per day was administered. In some cases the EEG discharge activity continued to be lowered even after the drug blood level had reached steady state. With medication, frequency and total duration of paroxysms were significantly lowered (by more than 90%) in over 80% of the patients, whereas the mean duration of paroxysmal activity did not change uniformly. Before treatment, short paroxysms (1-5 s) were seen together with longer ones in 11 patients. During treatment either all paroxysms disappeared or, in cases of remaining activity, most discharges were short and not accompanied by seizure manifestations. Blood level profiles over 24 h showed maximal values between midnight and 2 a.m. The minimal values (about half of the maximum) were found between 10 p.m. and midnight. The 8 a.m. value was 70-80% of the maximum. Only three patients complained of slight side effects (temporary drowsiness, loss of hair). Because of the simplified handling, the relatively low dose per day, and the few side effects, it seems possible that for primary generalized epilepsies once daily evening administration of sodium valproate is appropriate without diminishing the antiepileptic effect.

Effect of valproic acid treatment on spike-wave discharge patterns during sleep and wakefulness.

7 patients suffering from absences were recorded before antiepileptic treatment, in the early phase of valproate monotherapy and after having reached steady state. Recordings made with the Oxford-Medilog 4-channel cassette recorder were analyzed visually as well as by a computerized s-w pattern recognition approach, the latter facilitating quantification of pattern characteristics (number, amplitudes and duration of spikes and waves). Measurements were made separately for epochs of wakefulness and sleep. Compared to the premedication phase the amount of s-w discharges in 24 h showed an average reduction of more than 90%. For the majority of the patients, 24-hour discharge profiles showed a maximum in the early morning. Duration and amplitude of both spike and wave elements was higher during sleep. For the waking state, the ratio wave amplitude/spike amplitude was found to be increased under medication.