Biomedical subjects

G Krämer

Publications and source records attributed to G Krämer.

At least 19 recordsLinked to original sources

PubMed2006

Amygdala fMRI lateralizes temporal lobe epilepsy.

OBJECTIVE: To characterize the clinical value of an fMRI task activating the amygdala in controls and patients with mesial temporal lobe epilepsy (MTLE). METHODS: A fearful face fMRI paradigm using video sequences was developed and investigated in 17 patients with epilepsy (12 had MTLE [6 right- and 6 left-sided]) and 17 healthy control subjects. Reproducibility was demonstrated by reimaging 12 of the control subjects. In addition, parahippocampal activation was measured using Roland's Hometown Walking Task within the same session in all patients and in nine of the control subjects. RESULTS: A fearful face paradigm led to significant amygdala activation (p < 0.001) in all subjects. Amygdala activation was bilateral in control subjects and clearly lateralized in patients with MTLE. Dissociated amygdala and parahippocampal activation was found in three MTLE patients. A combination of results from both fMRI paradigms improved the lateralization of the side of seizure onset in patients with MTLE. CONCLUSIONS: fMRI activation of the amygdala evoked by an animated fearful face paradigm is strong, reproducible, and specific in individual subjects. The combination of the fearful face paradigm and Roland's Hometown Walking Task provides a more reliable presurgical mapping of mesial temporal lobe structures.

Adolescent↗

PubMed2006

[Neuropsychological outcome following intrauterine exposure to valproate].

A number of recent studies suggest a link between in utero exposure to valproate (VPA) and low IQ and behavioural disorders in children of mothers with epilepsy. In this review, a commission of the German Section of the International League Against Epilepsy discusses the evidence in the literature and practical recommendations for the use of VPA in women of childbearing potential. It is concluded that despite methodological shortcomings--largely due to the complexity of the problem and small case numbers in prospective studies--the existing data are sufficiently alarming to require great caution in the use of VPA in women who could become pregnant. The underlying mechanisms of how antiepileptic drugs may lead to neurodevelopmental problems are unclear. Further prospective studies are urgently needed to clarify this clinically important issue, and a collaborative study is suggested based on the international network established by the European Registry of Antiepileptic Drugs and Pregnancy.

Female↗

PubMed2006

Levetiracetam: a long-term follow-up study of efficacy and safety.

OBJECTIVES: To evaluate the efficacy and safety of long-term add-on treatment with levetiracetam 1,000-4,000 mg/day. PATIENTS AND METHODS: In this multicenter, open-label follow-up study, 505 patients, from 10 European countries, who had benefited from previous add-on treatment with levetiracetam in a clinical trial or compassionate-use program were enrolled; 274 (54.3%) stayed to the end. Most then continued levetiracetam by prescription or in a named patient program, where it was not yet commercially available. Mean treatment duration was 1,045 days (range: 24 days to >7 years). Median daily dosage was 3,000 mg/day (range: 250-6,000 mg/day), with 250 (49.5%) patients receiving levetiracetam for >3 years. RESULTS: Median total and partial seizure frequency per week over the evaluation period were 0.8 and 0.7; seizure frequency per week was generally stable over time and remained low. There was a probability of 6.6% of remaining seizure-free for the first 3 years, and of 18.9% of having a seizure-free period of at least 3 years at any time. Most adverse events were mild or moderate and unrelated to study drug. Levetiracetam was well tolerated, and provided stable seizure control during long-term treatment.

Adolescent↗

PubMed2006

Role of valproate across the ages. Treatment of epilepsy in the elderly.

In June 2005, a team of experts participated in a workshop with the objective of reaching agreement on several important aspects of valproate in the treatment of elderly patients with epilepsy. Epilepsy in the elderly is relatively common and its incidence increases for each decade after age 60. The aetiology and manifestations of epilepsies in the elderly are complex because of comorbidity and other underlying risk factors. A consensus was reached that elderly patients who present with a seizure disorder should be referred rapidly to a specialist and that diagnosis should be improved by using a multidisciplinary team of cardiologists, neurologists and epilepsy experts (syncope, falls and seizure specialists). This is especially important to avoid mistreatment with antiepileptic drugs (AEDs). There was consensus that the elderly are generally more susceptible to the adverse effects of AEDs than younger adults. For these reasons, in older persons AEDs should be started at low dosages, and titrated slowly according to clinical response. Some of the most troublesome side effects of AEDs in the elderly include sedation and cognitive side effects, as well as osteoporosis. Drug-drug interactions should be given special consideration. There was consensus that the pharmacokinetics of all AEDs are altered in the elderly, and that the most significant change common to all AEDs is a moderate reduction in renal and metabolic clearance. Predicting pharmacokinetic changes in the individual, however, can be very difficult because multiple factors contribute to a high inter-patient variability. There was agreement on the advantages and disadvantages of the use of valproate in the elderly, and consensus that valproate is a useful option in this population. There was no consensus, however, on whether valproate should be considered among the preferred first-line treatments in the elderly.

Aged↗

PubMed2004

Germline and mosaic mutations of FLN1 in men with periventricular heterotopia.

OBJECTIVE: To describe the phenotypic spectrum and genetics of periventricular nodular heterotopia (PNH) caused by FLN1 mutations in four men. BACKGROUND: X-linked PNH caused by FLN1 mutations (MIM #300049) implies prenatal or early postnatal lethality in boys and 50% recurrence risk in daughters of affected women. METHODS: Clinical examination, cognitive testing, MRI, and mutation analysis (denaturing high-performance liquid chromatography and direct sequencing) on blood lymphocytes and single hair roots were performed for nine affected individuals, including three men. Neuropathologic study of the brain was performed for an affected boy. RESULTS: In two families, missense mutations were transmitted from mother to son (Met102Val) and from father to daughter (Ser149Phe), causing mild phenotypes in both genders, including unilateral PNH. In a third family, a man was mosaic for an A>G substitution (intron 11 acceptor splice site) on leukocyte DNA and hair roots (mutant = 42% and 69%). Single hair root analysis confirmed that the mutation was not present in all ectodermal derivative cells. A healthy daughter had inherited the X chromosome from her father's wild-type germinal cell population. In the fourth family, an eight-base deletion (AGGAGGTG, intron 25 donor splice site) led to early deaths of boys. Postmortem study in a newborn boy revealed PNH and cardiovascular, genitourinary, and gut malformations. CONCLUSIONS: Periventricular nodular heterotopia caused by FLN1 mutations in men has a wide clinical spectrum and is caused by different genetic mechanisms, including somatic mosaicism. Mutation analysis of FLN1 should support genetic counseling in men with periventricular nodular heterotopia.

Abnormalities, Multiple↗

PubMed2002

Hyperandrogenism, postprandial hyperinsulinism and the risk of PCOS in a cross sectional study of women with epilepsy treated with valproate.

Among a sample of 43 women with epilepsy treated for at least 2 years with valproate (n=22) or other antiepileptic drugs (AEDs) (n=21), polycystic ovary syndrome (PCOS) was diagnosed in three women, two of them were treated with valproate. Although the rate of PCOS and of menstrual disturbances, weight body mass index (BMI) and waist to hip ratio as well as fasting blood glucose levels, fasting insulin, proinsulin and C-peptide values was similar in this small sample of women treated with valproate and other AEDs, valproate exposure was associated with higher androgen levels, higher postprandial (pp) insulin and proinsulin levels, as well as lower cholesterol and low density lipoprotein (LDL) cholesterol levels. The pronounced increase in pp insulin levels during VPA treatment may indicate an effect of the fatty acid derivate VPA on pancreatic islet cells.

Adult↗

PubMed2001

Simultaneous determination of olanzapine, clozapine and demethylated metabolites in serum by on-line column-switching high-performance liquid chromatography.

An automated method for simultaneous routine quantification of the antipsychotic drugs clozapine, olanzapine and their demethylated metabolites is described. The method included adsorption on a cyanopropyl (CPS) coated clean-up column (10 microm; 10 x 2.0 mm I.D.), washing off interfering serum constituents to waste, and separation on C18 ODS Hypersil reversed phase material (5 microm; 250 x 4.6 mm I.D.) using acetonitrile-water-tetramethylethylenediamine (37:62.6:0.4, v/v/v) adjusted to pH 6.5 with concentrated acetic acid. UV-detection was performed at 254 nm. The limit of quantification was 10-20 ng/ml. Relative day to day standard variations ranged between 4.5 and 13.5%. The method is suitable for routine monitoring of olanzapine and clozapine including their demethylated metabolites.

Antipsychotic Agents↗

PubMed2001

Epilepsy and trisomy 19q--different seizure patterns in a brother and a sister.

In symptomatic epilepsies due to chromosomal aberrations, epileptogenesis may be either the direct consequence of deletion or duplication of a gene causing seizures or may have a more complex etiology caused by the disturbance of the interaction of several genes and environmental factors. We report on a brother and a sister with trisomy 19q13.3-->qter who present different epileptologic features and discuss epileptogenesis in this syndrome with respect to genes known to be located on the distal part of chromosome 19q. Both patients share mental retardation and several dysmorphic features. The boy was hypoxic at birth and showed an extremely delayed psychomotor development. The girl, however, had no significant neonatal problems, and her psychomotor development was better. Although the male had an abnormal EEG in childhood, his first partial seizures occurred only as late as at age 31 years. He subsequently became seizure-free with carbamazepine (CBZ). In contrast, the girl already suffered from absence-like seizures during childhood and became seizure-free under ethosuccimide (ESM). A photoparoxysmal response, however, is still visible in her EEG. The difference between the epileptologic features in these siblings points to epileptogenic mechanisms placed far downstream on the way from genotype to phenotype. The photoparoxysmal response--otherwise a facultative finding in genetically determined epilepsies--in the EEG of the sister, however, points to a closer relationship between the duplicated genes and epileptogenesis. The fact that genes encoding potassium channels are located on 19q13.3-q13.4 may also support the latter assumption.

Adult↗

PubMed2001

[Epileptic seizures and epilepsy in the elderly].

Contrary to former views the incidence rate of epilepsies after age 65 are higher than in childhood and adolescence and epileptic seizures are one of the most common neurological problems in the elderly. The most common seizure types are primary focal with possible secondary generalization in about two thirds of the patients, the most common etiology are cerebrovascular disturbances, brain tumors, head injuries and degenerative diseases. Todd's pareses or other postictal disturbances are quite common. This article covers diagnostic and therapeutic aspects with special consideration of the influence of accompanying diseases (especially of the liver and kidneys) on the pharmacotherapy.

Adolescent↗

PubMed2001

Recommendations on the clinical use of oxcarbazepine in the treatment of epilepsy: a consensus view.

Extensive clinical use and a series of clinical trials have shown that oxcarbazepine is a valuable antiepileptic drug for the treatment of adults and children with partial onset seizures both in initial monotherapy, for conversion to monotherapy and as adjunctive therapy. The clinically recommended titration scheme for all forms of therapy in adults is to start with 150 mg/day at night and to increase by 150 mg/day every second day until a target dose of 900-1200 mg/day is reached. If necessary, one can go faster and start with up to 600 mg/day and titrate with weekly increments of up to 600 mg/day. In children, treatment can be initiated with 8-10 mg/kg/day body weight in two to three divided doses. Dosage can be increased by 8-10 mg/kg/day in weekly increments if necessary for seizure control. Hyponatremia (serum sodium <125 mmol/l) can develop gradually during the first months of oxcarbazepine therapy in approximately 3% of patients with a previously normal serum sodium. However, there is no need to measure baseline serum sodium concentrations unless the patient has renal disease, is taking medication which may lower serum sodium levels (such as diuretics, oral contraceptives or nonsteroidal anti-inflammatory drugs) or--in rare cases--has clinical symptoms of hyponatremia. During oxcarbazepine maintenance therapy measurement of serum sodium levels should also be considered if medications known to decrease sodium levels are added or symptoms of hyponatremia develop. Oxcarbazepine does not appear to have any clinically notable effects on other safety parameters such as renal and liver function or haematological test results. In summary, oxcarbazepine is a safe and well tolerated antiepileptic drug for partial epilepsy.

Anticonvulsants↗

PubMed2001

Epilepsy in the elderly: some clinical and pharmacotherapeutic aspects.

The majority of epileptic seizures and epilepsies are no longer manifested in childhood and adolescence; instead their incidence is higher at the age of 65 years or older than during the first two decades of life. After cerebrovascular disorders and dementias, epileptic seizures and epilepsies now constitute the third most frequent neurologic problem encountered in the elderly. Important clinical features of epilepsy in the elderly related to the diagnosis include the most common seizure types and causes. Special features of drug treatment for epilepsy in the elderly result not only from the physiologic changes in the elderly but also from the particular pharmacology of the respective drugs. Because elderly patients very often require other long-term medication in addition to antiepileptic therapy, drug interactions between different antiepileptic drugs and between antiepileptics and other drugs can be of major significance. Other special features of pharmacotherapy for epilepsy in the elderly include the presence of liver and kidney diseases.

Age Factors↗

PubMed2000

[Drug therapy before and after surgery for epilepsy. Critical review and recommendations].

As a result of a critical review of the literature and a survey at German epilepsy centers of usual pre- and postoperative drug treatment, the following strategy is recommended: 1. Patients under consideration for surgery should be referred to specialists. Experience has shown that surgery is reasonable for only about a third of all patients with refractory epilepsies. The patient should first have been treated for at least 3 years with at least two first-line drugs in monotherapy and subsequent combined therapy. This applies only to medial temporal lobe epilepsies with very good postoperative prognoses. All other surgically removable epilepsy syndromes with less positive prognosis should be treated with additional antiepileptic drugs before any surgery. 2. There is no exception to the continuation of drug treatment after epilepsy surgery. If the patient remains free of seizures for at least 2 years, discontinuing the drug treatment can be discussed, just as with patients who are free of seizures due to drug treatment alone. In general, the less successful the operative therapy, the longer and more intensive the drug treatment.

Adult↗

PubMed2000

The pyrrole moiety as a template for COX-1/COX-2 inhibitors.

Aroyl- and thiophene-substituted pyrrole derivatives have been synthesized as a new class of COX-1/COX-2 inhibitors. The inhibition of COX-1 was evaluated in a biological system using bovine PMNLs as the enzyme source, whereas LPS-stimulated human monocytes served as the enzyme source for inducible COX-2. The determination of the concentration of arachidonic acid metabolites was performed by HPLC for COX-1 and RIA for COX-2. Variation of the substitution pattern led to a series of active compounds which showed inhibition for COX-1 and COX-2. Structural requirements for the development of COX-1/COX-2 inhibitors are discussed.

Animals↗

PubMed2000

Tiagabine in the treatment of epilepsy--a clinical review with a guide for the prescribing physician.

Tiagabine is currently recommended mainly as add-on therapy in adults and children above 12 years with partial epilepsy not satisfactorily controlled with other antiepileptic drugs. Based on available evidence and our clinical experience, tiagabine should be used preferably in patients sharing one or more of the following additional features, (i) a history of drug-induced cutaneous adverse events; (ii) mild to moderate epilepsy allowing for a slow titration and gradual onset of anticonvulsant action over a few weeks; (iii) patients for whom it is particularly important to avoid a deterioration in cognitive performance; and, (iv) patients who failed to respond to previous treatment with sodium channel blocker agents as they may particularly benefit from the introduction of tiagabine, due to its GABAergic mechanism of action. Tiagabine can also be used successfully in other patients with refractory partial epilepsy. Tiagabine is not indicated for patients with generalized or unclassified epilepsies and for patients with severely impaired liver function.

Adult↗

PubMed2000

From clinical observation to long-term monitoring: diagnostic developments in conservative epileptology.

The diagnostic goals in nonsurgical (conservative) epileptology differ from presurgical diagnostic aims. The resulting development of diagnostic methods in a tertiary-level epilepsy center is shown and the major technical and organizational consequences of this difference for diagnostic long-term monitoring (LTM) as opposed to presurgical LTM are investigated. A total of 133 consecutive daytime LTM investigations using radio telemetry were reviewed and seizure parameters such as type, duration, method of seizure detection, and need of mobility were evaluated and compared to presurgical LTM. Compared to presurgical LTM, partial seizures were relatively rare (17.8%) and short epileptic or nonepileptic motor events lasting <1 s, such as myoclonic, atonic, short tonic seizures, spasms, tics, or startle reactions, are frequent (34.9%). Of all seizures, 23% had no or minor ictal EEG changes, subtle symptomatology without signaling by a patient or accompanying person, and could be detected only by continuous online surveillance by an experienced EEG technician. Due to the nature of the patient population in diagnostic LTM, there is an increased need for ictal and interictal mobility (radio telemetry). LTM in conservative epileptology requires more intense human surveillance for seizure detection and increased patient mobility compared to presurgical LTM.

Adolescent↗

PubMed2000

Twenty years of ictal EEG-EMG.

This study aimed to evaluate the use of ictal EEG recordings combined with simultaneous surface EMG in the diagnosis and analysis of motor events, both epileptic and nonepileptic. All ictal registrations were performed utilizing radio/cable telemetry. Routine recordings consisted of 18-channel EEG plus 8-channels bipolar surface EMG in freely moving patients. Combined ictal EEG-EMG recordings in freely moving patients enabled us to identify and define the following pathomechanisms of epileptic drop seizures, epileptic axial spasms, atonic, myoclonic-atonic, and akinetic seizures. Precise differentiation could be made between tonic and nontonic postural seizures and between startle-induced reflex seizures and hyperekplexia. The findings from telemetered ictal recordings in freely moving patients with combined EEG and surface EMG offer the only means of identifying, defining, and differentiating motor events, both epileptic and nonepileptic, of a short duration that cannot be properly differentiated by clinical examination alone.

Diagnosis, Differential↗

PubMed1999

[Serum concentration of anticonvulsants. Practical guidelines for measuring and useful interpretation. Therapy Committee of the German Section of the International Epilepsy League].

The clinical relevance of being informed on the serum concentration of antiepileptic drugs has been judged very differently during the last decades. Therefore the Commission on the treatment of epilepsy (German section of the International League against Epilepsy) had the task to outline the importance of therapeutic monitoring of anticonvulsant serum concentrations. The possibility of determining the serum concentration of anticonvulsants induced the elaboration of "therapeutic drug level ranges". The usefulness of determining serum concentrations of antiepileptic drugs in clinical management of patients with epilepsy depends decisively on the following questions: Can the efficacy of antiepileptic drug treatment be increased by serum concentration monitoring? Can the rate of adverse effects of antiepileptic drugs be reduced by serum concentration monitoring? Clinical experience suggests numerous indications of therapeutic drug monitoring, scientific studies however, supporting these empirical guidelines are not available. Therefore, therapeutic drug monitoring may be restricted for some special situations which have to be justified in every single case. Tailored determinations with specific purposes are e.g.: resistance to therapy, including suspected irregular intake; suspected intoxication, particularly during combined therapy; the possibility of significant changes in the dosage-serum concentration relationship (interactions with other drugs, unusual pharmacokinetics in childhood, in pregnancy etc.).

Adult↗

PubMed1999

Medical technology assessment photic stimulation--standardization of screening methods.

RATIONALE: In many EEG laboratories in Europe, intermittent photic stimulation (IPS) is not performed routinely, and consequently, great variation exists in the type of photo stimulator used, the methodology employed, and the interpretation of the EEG curves, thus leading to different outcomes. METHODOLOGY: It was decided to hold a consensus meeting with experts in the field of photic stimulation from various European countries. This meeting was held at the Stichting Epilepsie Instellingen Nederland, Heemstede, the Netherlands. The consensus reached was presented and discussed at the 9th European Congress of Clinical Neurophysiology in Ljubjana in June 1998. RESULTS: Patients should be positioned at a distance of 30 cm from the photic stimulator (nasion to lamp) with dim surrounding lights, just enough to see the patient. Flashes should be delivered in separate trains of 10 s for each frequency, with intervals of 7 s minimum. First stimulation occurs with eyes open followed after 5 s by eye closure, while starting at 1 Hz progressing to 20 Hz, unless generalised epileptiform discharges are evoked at a lower frequency. Then, frequencies should start at 60 Hz decreasing to 25 Hz. The following frequencies should be used: 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 60, 50, 40, 30 and 25 Hz. The total duration is a maximum of 6 min (patients without a reaction to IPS). In interpreting the evoked responses, a clear distinction should be made between epileptiform responses confined to the occipital area (OSW), starting occipitally and spreading to frontal regions (OGSW), or generalised from the start (GSW). Other responses include generalised spikes (OR). CONCLUSION: This standard is safe, relatively quick, simple and reliable. Comparison of data within patients and between patients of various laboratories will also be possible. This will improve the quality of the care of the individual patient and make collaborative research possible.

Electroencephalography↗