Biomedical subjects

B J Steinhoff

Publications and source records attributed to B J Steinhoff.

At least 55 records · Page 3Linked to original sources

PubMed1997

A double-blind controlled clinical trial: oxcarbazepine versus sodium valproate in adults with newly diagnosed epilepsy.

Oxcarbazepine (OXC) has been licensed as monotherapy and add-on treatment in epilepsy patients with partial seizures with or without secondarily generalized seizures (PS) and generalized tonic-clonic seizures without partial onset (GTCS). Its use as monotherapy in adults with newly diagnosed epilepsy was investigated in a double-blind, randomized, parallel-group comparison with sodium valproate (VPA). Two-hundred and forty-nine patients with either PS or generalized seizures aged 15-65 years were randomized. After a retrospective baseline, patients were randomized to VPA or OXC in a 1:1 ratio. The double-blind treatment phase was divided into two periods, flexible titration and maintenance. The titration period was 8 weeks followed by 48 weeks of individualized, maintenance treatment given three times a day. Three primary analyses were used to assess efficacy, tolerability, and the association between the two. In the efficacy analyses comprising 212 patients who had at least one seizure assessment during the maintenance period, no statistically significant difference at the 5% level was found between the treatment groups. Sixty patients (56.6%) in the OXC group and 57 patients (53.8%) in the VPA group were seizure free during maintenance treatment. Fifty-two patients in the OXC group discontinued treatment prematurely (15 because of tolerability reasons) compared to 41 patients in the VPA group (ten due to tolerability reasons). There was no statistically significant difference between the treatment groups with respect to the total number of premature discontinuations or those due to adverse experiences. This trial provides support for the efficacy and safety of OXC as first-line treatment in adults with PS and GTCS.

Adolescent↗

PubMed1997

The influence of established and new antiepileptic drugs on visual perception. 1. A placebo-controlled, double-blind, single-dose study in healthy volunteers.

The influence of single oral dosages of carbamazepine (CBZ), valproic acid, vigabatrin (VGB), lamotrigine (LTG), gabapentin (GBP), and losigamone (LSG) on visual perception was investigated in ten healthy volunteers according to a double-blind, placebo-controlled, cross-over study design. The test battery comprised visual acuity, the Lanthony-D-15-désaturé colour perception test, increment, postadaptation and transient tritanopia threshold measurements, perception threshold assessment for monochromatic and chromatic gaussian dots, monochromatic gratings and gratings of differing spatial frequency, and critical flicker fusion tests with various stimuli. The only consistent and partly significant effects were seen after VGB and GBP. After VGB, increment, postadaptation and transient tritanopia thresholds and the critical flicker fusion increased, whereas GBP led to a somewhat converse profile. The other tests were not influenced consistently by any antiepileptic drug (AED). We conclude that: (i) gamma-amino-butyric acid-(GABA)-related properties as under the prototype drug VGB result in specific alterations of the transient tritanopia phenomenon which is consistent with the physiological hypothesis for this retinal paradigm based on extracellular recordings in primates. The possible mechanisms why VGB improved critical flicker fusion as the only AED in this trial are discussed. The profile of GBP indicates a unique mechanism of action. We have not observed specific influences on visual perception under AEDs which act mainly via alterations of ion membrane conductance. The transient tritanopia and flicker fusion paradigms we used appear to be promising to investigate antiepileptic drugs with hitherto unknown modes of actions in human noninvasively.

Adaptation, Ocular↗

PubMed1997

The influence of established and new antiepileptic drugs on visual perception. II. A controlled study in patients with epilepsy under long-term antiepileptic medication.

In this study, we investigated visual performance under chronic antiepileptic drug treatment. Patients were under carbamazepine (CBZ) (n = 18), valproic acid (VPA) (n = 9), CBZ and vigabatrin (VGB) (n = 4), CBZ and gabapentin (GBP) (n = 8), and under CBZ and topiramate (TPR) (n = 6), respectively. Seven untreated patients with epilepsy and 42 healthy volunteers served as controls. The test battery comprised the Lanthony-D15-désaturé colour perception test, increment, postadaptation and transient tritanopia (TT) threshold measurements, visual perception threshold assessments for monochromatic and chromatic gratings and gaussian dots, and critical flicker fusion (CFF) tests. No differences were seen between naive patients and healthy controls. Patients under drug treatment always showed alterations of visual perception. Postadaptation and TT thresholds were altered under each drug regimen after short delays between switching off the adaptation light and switching on the blue test light. Threshold elevations were maximum under the combination of CBZ and TPR and lowest under CBZ and GBP. Consistent impairment of the CFF was seen under combined CBZ and TPR whereas VPA as well as combined CBZ and VGB led to ameliorations the mechanisms of which are discussed. The other tests were less sensitive. In conclusion, alterations of visual function were apparent under chronic antiepileptic drug treatment both with established and new agents. However, it may be difficult to distinguish between effects based on specific modes of action and nonspecific retino- and neurotoxicity.

Adaptation, Ocular↗

PubMed1997

Isolated ataxia as an idiosyncratic side-effect under gabapentin.

Gabapentin has been accepted worldwide as a novel antiepileptic drug with a favourable tolerability profile. However, movement disorders have been reported previously as rare side-effects in individual patients. We report on two patients who developed isolated severe ataxia under low-dose gabapentin which resolved abruptly after discontinuation of the drug. This side-effect probably resembled a rare idiosyncratic adverse reaction. We propose the gabapentin-specific neuronal binding site which has a high density in the cerebellum as a possible mechanism of action and suggest that the initiation of gabapentin requires caution if pre-existing cerebellar function impairment is evident.

Acetates↗

PubMed1997

Physical activity and fitness in patients with headache disorders.

Recent studies indicate that aerobic activities might reduce severity and/or frequency of migraine attacks. The present study was intended to investigate whether physical activities and fitness (aerobic endurance, flexibility, and muscle strength endurance) as well as body composition are different in patients with headache disorders and healthy control subjects. The study included 56 patients (aged 17-64 years) with headache disorders (migraine, tension-type, cluster, analgetics abuse, and other types of headache) and 145 age-matched volunteers without history of recurrent or chronic headache. A standardized questionnaire revealed similar self-esteem of physical activities in both groups. Objective physical fitness testing in a representative sample of 22 patients and 36 control subjects showed significantly reduced aerobic endurance in female and male patients as well as reduced flexibility in female patients as compared to control subjects, whereas muscle strength endurance was not significantly different between both groups. Female patients presented with a significantly higher total body fat as compared to control subjects. In conclusion, headache patients turned out to be less physically fit than control subjects. There was a discrepancy between self-esteem and objective test results regarding physical activity and fitness in patients with headache disorders.

Adolescent↗

PubMed1996

[123I]IBZM SPET analysis of dopamine D2 receptor occupancy in narcoleptic patients in the course of treatment.

Elevated levels of central D2 dopamine receptors were found on postmortem examination in cases of human narcolepsy. In vivo investigations using positron emission tomography (PET) and single photon emission tomography (SPET) found no changes of D2 binding in the striatal structures. To investigate whether the elevated D2 receptors in postmortem investigations are due to long-term treatment effects, we applied 123I-labeled (S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide (IBZM) ([123I]IBZM, a highly selective CNS D2 dopamine receptor ligand) and SPET in narcoleptic patients in the course of treatment with stimulants and/or antidepressants. Before treatment we found no changes in D2 binding in 10 patients (in comparison to 10 normal controls). After treatment (performed in five patients for 3 months) we found changes in D2 binding in four of them, indicating that the results of the postmortem studies could have been influenced by long-term medications. Human narcolepsy seems not to be related to a striatal D2 dopaminergic disturbance.

Adolescent↗

PubMed1996

Accuracy and reliability of periodic sharp wave complexes in Creutzfeldt-Jakob disease.

OBJECTIVE: To assess the sensitivity, specificity, and interobserver reliability of periodic sharp wave complexes in the electroencephalograms of patients with Creutzfeldt-Jakob disease. DESIGN: Sixty-eight electroencephalograms in 29 patients who had been suspected of having Creutzfeldt-Jakob disease were reanalyzed by an investigator who was unaware of the clinical data. The incidence of periodic sharp wave complexes in neuropathologically confirmed Creutzfeldt-Jakob disease vs progressive dementia other than Creutzfeldt-Jakob disease was assessed. Blinded electroencephalogram analysis was performed by a second investigator. The interobserver reliability was assessed by the kappa value. SETTING: University hospital, base of the German National Creutzfeldt-Jakob Disease Surveillance Study. PATIENTS: Fifteen patients with neuropathologically confirmed Creutzfeldt-Jakob disease and 14 patients who had been suspected of having Creutzfeldt-Jakob disease because of rapidly progressive dementia but in whom other dementias were diagnosed by unblinded investigators based on clinical and electroencephalographic criteria. MAIN OUTCOME MEASURE: Sensitivity and specificity of periodic sharp wave complexes assessed by their incidence in Creutzfeldt-Jakob disease vs other dementias. Interobserver reliability of periodic sharp wave complexes was expressed by the kappa value. RESULTS: For periodic sharp wave complexes, blinded electroencephalographic analysis resulted in a sensitivity and a specificity of 67% and 86%, respectively. Interobserver reliability was excellent (kappa = 0.95). CONCLUSION: This blinded electroencephalographic study in Creutzfeldt-Jakob disease confirms the high diagnostic value of electroencephalography, as previously reported by open studies.

Aged↗

PubMed1996

Effects of antiepileptic drugs on motor cortex excitability in humans: a transcranial magnetic stimulation study.

The effect of a single oral dose of various antiepileptic drugs on the excitability of the motor system was studied in healthy volunteers by means of transcranial magnetic stimulation. Motor threshold, duration of the cortical silent period, and intracortical excitability after double-shock transcranial stimulation were tested before and at defined intervals after drug intake. Antiepileptic drugs that support the action of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the neocortex (vigabatrin, baclofen) reduced intracortical excitability but had no effect on motor threshold. Gabapentin, whose mechanism of action has not yet been unequivocally identified, showed a similar profile. By contrast, sodium and calcium channel blockers without considerable neurotransmitter properties (carbamazepine, lamotrigine, losigamone) elevated motor threshold but did not change intracortical excitability. The cortical silent period was lengthened by gabapentin and carbamazepine. Changes in peripheral motor excitability (maximum M wave, peripheral silent period) were not observed. We conclude that the changes in intracortical excitability are caused by GABA-controlled interneuronal circuits in the motor cortex while changes in motor threshold are dependent on ion channel conductivity and may reflect membrane excitability. Transcranial magnetic stimulation may be a promising noninvasive approach to study the selective effects of antiepileptic drugs on brain function.

4-Aminobutyrate Transaminase↗

PubMed1996

The effect of lorazepam on the motor cortical excitability in man.

The effect of the short-acting benzodiazepine lorazepam on motor cortex excitability was investigated in 11 healthy volunteers using the technique of focal transcranial magnetic stimulation. The threshold intensity for evoking an electromyographic response in the resting and active abductor digiti minimi muscle, the size of the motor evoked potential, the duration of the cortical and peripheral silent periods, the corticocortical inhibition and facilitation after paired magnetic stimuli, and the transcallosal inhibition were used as parameters to assess various aspects of motor system excitability. Baseline values were compared with data obtained 2, 5 and 24 h after a single oral dose of 2.5 mg lorazepam. Resting and active motor thresholds and the size of the motor evoked potential remained unchanged. The duration of the cortical silent period was prolonged with a maximum effect 5 h after drug intake, while the peripheral silent period did not show any lengthening at that time. The corticocortical inhibition showed a tendency toward more inhibition, while the corticocortical facilitation was almost completely suppressed. The transcallosal inhibition showed an inconsistent trend to less inhibition. In parallel to the pharmacokinetics of lorazepam, all effects peaked at 2 h and 5 h, and were (partially) reversible after 24 h. It is hypothesized that most of these findings are due to the reinforcement of GABA action by lorazepam at the level of the motor cortex. The lack of effect on motor threshold and on the size of the motor evoked potential may indicate that these parameters are physiologically distinct from corticocortical excitability and the cortical silent period. The relevance of the present data in clinical epileptology is discussed.

Adult↗

PubMed1996

The effect of anti-epileptic drugs on visual perception in patients with epilepsy.

We investigated the influence of the antiepileptic drugs carbamazepine (CBZ), phenytoin (PHT) and valproic acid (VPA) on different aspects of visual perception in patients with epilepsy by three different methods. (i) The colour arrangement test Farnsworth Munsell D100. (ii) A monitor system generating 24 different Gaussian dots and 24 different vertical sinusoidal gratings. Luminance increments and decrements for achromatic discrimination and four different colours for chromatic discrimination were investigated with four different sizes each adding up to 24 stimuli. (iii) A Maxwellian view system providing a foveal blue test light either superimposed on a yellow adaptation field (increment threshold) or after switching off this field (postadaptation threshold). Five different adaptation levels were investigated. Patients on PHT offered the most abnormalities, particularly in the D100 and in all Gaussian dots recordings. The individual differences between increment and postadaptation threshold (transient tritanopia effect) were significantly elevated at the four higher adaptation levels, whereas no change was found in the increment thresholds and only for the highest luminance level in the postadaptation thresholds. With VPA, chromatic and achromatic increment discrimination was impaired particularly for larger Gaussian stimuli on the monitor system. Valproic acid also induced a consistent increment threshold increase on the Maxwellian view system, an increase of the postadaptation threshold at the highest luminance level and, like PHT, an increase of the threshold differences at level 3 and 4, but not at the highest background level 5. Patients on CBZ provided normal results in all investigations, with the exception of a slight but significant increase in the D100 error score. Sinusoidal gratings turned out to be much less sensitive than Gaussian dots since they remained unchanged in patients on all three drug groups.

Adult↗

PubMed1996

Leisure time activity and physical fitness in patients with epilepsy.

PURPOSE: To assess social and physical activity by means of a controlled study based on a questionnaire and standardized clinical tests of physical fitness. METHODS: In this controlled study, we assessed several issues of social and physical activity in 136 patients with epilepsy and 145 controls by using a questionnaire. In addition, we investigated physical fitness based on physical parameters such as body mass index and body composition and standardized tests of aerobic and muscle strength endurance and physical flexibility in 35 adult patients and 36 healthy controls. RESULTS: Leisure time habits both at home and outside the home were mainly similar except for visits of friends, which were significantly reduced in patients. Although the general attitude toward sports and physical activity was positive in both groups, and although controls judged sports to be dangerous significantly more often (p = 0.007), controls participated in regular sports significantly more frequently (p = 0.005). The clinical study demonstrated a lack of physical fitness, as suggested by the questionnaire data. Statistical analysis demonstrated significant differences of aerobic endurance (p < 0.001), muscle strength endurance (p < 0.001), and physical flexibility (p < 0.001) in favor of the control subjects. The body mass index was significantly higher in patients (p = 0.03), whereas the body composition revealed a higher body fat ratio only in female patients (p = 0.04). CONCLUSIONS: We conclude that patients with epilepsy suffer from a considerable lack of physical fitness that might have an important impact on their general health and quality of life. In addition to overprotection and reduced mobility, the questionnaire revealed insufficient knowledge among health professionals and sport instructors as a major factor contributing to these results.

Adolescent↗

PubMed1996

Ictal near infrared spectroscopy in temporal lobe epilepsy: a pilot study.

Near infrared spectroscopy (NIRS) is a non-invasive method to measure cerebral tissue oxygenation continuously with an adhesive optode system which can be easily placed on the skin. We coupled NIRS with video-electroencephalography (video-EEG) during the presurgical evaluation of two patients with intractable localization-related epilepsy of mesial temporal origin. Cerebral oxygen saturation was measured either ipsilaterally (three seizures) or contralaterally (four seizures) to the primary epileptogenic zone. Since NIRS measures cerebral tissue oxygenation in a depth of only few centimetres, it did not record within the primary epileptogenic zone in our patients. Therefore we decided to place the NIRS optodes comfortably for the patients on the hairless skin corresponding with measurement of the oxygenation within the corresponding frontal cortex. Ipsilateral measurement revealed a marked desaturation in the course of the seizure with a postictal maximum whereas contralateral findings were inconsistent. The favourable outcome of selective amygdalahippocampectomy in both cases retrospectively confirmed the correct lateralization by video-EEG and the concordant NIRS findings. Our preliminary results suggest that NIRS might be a simple, cost-effective and non-invasive additional method to lateralize the primary epileptogenic zone in temporal lobe epilepsy and should be further investigated in larger series of patients.

Adult↗

PubMed1995

Changes of central benzodiazepine receptor density in the course of anticonvulsant treatment in temporal lobe epilepsy.

The first investigation of the central-type benzodiazepine (BZ) receptor density before and following 2 months successful treatment with carbamazepine (CBZ) in a patient with temporal lobe epilepsy (TLE) using 123I-labelled Iomazenil (a specific lipophile central BZ receptor compound) and single photon emission tomography (SPET) is reported. First, a focal slowing of the EEG in the left temporal area was noted and a corresponding reduction of the central BZ density of the left temporal lobe was found. After 2 months of treatment the patient was symptom-free, and a normal BZ receptor density and no pathological EEG signs were found. The increase in central BZ receptor binding sites might be related to the anticonvulsant effects of CBZ mediated by the so-called peripheral BZ receptor sites.

Adult↗

PubMed1995

Ictal scalp EEG in temporal lobe epilepsy with unitemporal versus bitemporal interictal epileptiform discharges.

We investigated the ictal scalp EEG in 228 seizures of 36 patients with unitemporal (n = 25) or bitemporal independent (n = 11) interictal epileptiform discharges (IED). All patients had proven temporal lobe epilepsy since they became seizure-free or only had auras after temporal lobectomy with a minimum follow-up of 1 year. Ictal patterns at seizure onset or later in the course of the seizure were lateralized significantly more often in patients with unitemporal IED (90%, at seizure onset and 96%, later) compared with those with bitemporal independent IED (75%, at seizure onset and 78%, later). Furthermore, scalp ictal EEGs, when lateralized at seizure onset or later in the course of the seizure, were significantly more likely to predict the correct side for surgery in patients with unitemporal (98%, at seizure onset and 100%, later) than bitemporal (64%, at seizure onset and 77%, later) IED. Bilateral independent seizure onsets, asynchrony of ictal activity over the two temporal lobes, and switch of ictal activity from one to the other hemisphere are ictal patterns that are strongly correlated with bitemporal excitability.

Adolescent↗

PubMed1994

[The pharmacologic and clinical profile of the new anticonvulsant felbamate--an overview].

Felbamate is a new anticonvulsant which has already been marketed in some countries outside Germany, i. e., in the United States. Since marketing in Germany is in progress, one may soon expect felbamate to be in clinical use. Both the chemical structure and the probable mechanism of action are different from the currently available antiepileptic drugs. The studies already published allow to expect felbamate to improve substantially the possibilities of antiepileptic pharmacotherapy, since it is an anticonvulsant with a high efficacy in the treatment of partial epilepsy and especially with a very good tolerability. Its disadvantage are numerous interactions with other antiepileptic drugs. This article is an update review of the literature on felbamate.

Adult↗

PubMed1994

[Cardiac side effects and ECG changes with lamotrigine?--A clinical study].

After a patient treated with lamotrigine (LTG) had suffered from thoracal pain and repolarisation deficiencies in the electrocardiogram (ECG), we prospectively investigated 20 patients with localization-related epilepsies to assess cardiovascular side effects of LTG. During the study, LTG was added to a stable dosage of one to three first line antiepileptic drugs (AED). Physical examinations and ECG recordings were performed regularly. Clinical cardial side effects did not occur. Only in single ECG traces of six patients non specific abnormalities were seen. Only in one patient, the abnormalities (supraventricular extrasystoles and a first grade atrioventricular block) unequivocally appeared initially under LTG. However, in the same patient two later ECG recordings under higher LTG dosages were normal. The statistical analysis of the ventricular activation times did not reveal any significant changes under LTG (p = 0.05) with the exception of an extended PQ time when comparing a patient group before LTG (n = 11) with another patient group under LTG (n = 11). Since this observation was not confirmed by the statistical analysis of a third patient group (n = 10) with ECG data prior to and under LTG, we believe that the statistically significant changes mentioned above were based mainly on structural differences between the patient groups and not on true LTG effects. Our results do not give evidence for an elevated risk of clinically relevant cardial side effects under LTG.

Adolescent↗

PubMed1994

[Variants of Todd's paralysis: postictal apraxia and prolonged postictal hemineglect].

Todd's post-epileptic paralysis is a well-known complication after focal or generalized epileptic seizures. The underlying pathophysiology, however, is still unknown. Commonly, it is associated with a hemiparesis, usually lasting minutes or hours, rarely as long as two days, with subsequent complete remission. We report 2 patients with unusual and variant post-epileptic syndromes which have not been previously described in the literature: first, an ideomotor limb apraxia, and second, a severe hemineglect syndrome. Each syndrome lasted up to 70 hours after the seizure and was completely reversible.

Adult↗

PubMed1993

Temporary abolition of seizure activity by flumazenil in a case of valproate-induced non-convulsive status epilepticus.

We report on a 33-year-old female suffering from frequent complex-partial seizures who developed a non-convulsive status epilepticus after one week of antiepileptic therapy with valproate (VPA) which had been added to a basic medication with barbexaclone (BBC) in rapidly increasing dosage. The electroencephalogram (EEG) showed continuous rhythmic generalized sharp and slow wave activity with a frontal maximum. Intravenous administration of 3.0 mg of the benzodiazepine (BZ) receptor antagonist flumazenil under monitoring with video-EEG led to an immediate and marked electroclinical improvement, whereas 6.0 mg of the BZ receptor agonist midazolam was followed by a deterioration both clinically and in the EEG. We discuss the concept of VPA-encephalopathy and the possible mechanisms of the action of flumazenil on VPA-induced as well as on other toxic and metabolic encephalopathies. Flumazenil might antagonize increased benzodiazepine receptor activity with agonistic and even convulsive properties in these encephalopathic syndromes. Further investigations are needed concerning the relation of drug-induced or metabolic encephalopathies and central benzodiazepine receptor activity. We recommend a therapeutic trial with flumazenil, if stupor or decreased seizure control develop in patients treated with valproate.

Adult↗