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Biomedical subjects

W Fröscher

Publications and source records attributed to W Fröscher.

At least 37 records · Page 2Linked to original sources

[The course of pregnancy and teratogenicity of antiepileptic agents in 66 patients with epilepsy].

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.

Abnormalities, Drug-Induced↗

Sleep and prolonged epileptic activity (status epilepticus).

The correlations between sleep and prolonged epileptic activity are discussed on the basis of the status classification of Gastaut (1983). Little information is available on the interrelation of sleep and the status of tonic-clonic seizures (grand mal status). Most important is the therapeutical management of these cases. Tonic seizures have been reported to occur in large numbers during NREM sleep in patients with Lennox-Gastaut syndrome. A status-like increase is possible. Tonic seizures occur almost exclusively during sleep. Myoclonic status epilepticus arising (a) in the course of primary generalized epilepsy and (b) in the course of encephalopathies, are usually markedly attenuated during sleep. In absence status (petit mal status) synchronized sleep generally fragments the continuous discharge which is replaced by isolated bursts of polyspikes, or polyspike and wave complexes. The absence status can recur upon awaking during the night or in the morning. The abnormal EEG activity of a petit mal status can, however, occasionally persist during the whole night. Improvement as well as activation during sleep have been observed in elementary (= simple) partial status epilepticus; improvement seems to be more frequent. Epilepsia partialis continua may persist or decrease during sleep. An increase as well as decrease of motor phenomena has been observed during the REM stages. 'Epileptic aphasia' of childhood is associated with subclinical bioelectric status epilepticus during sleep. The electrical status epilepticus must be delineated as a separate group. The term encephalopathy related to electrical status epilepticus during slow sleep (ESES) has been proposed on the basis of associated psychic syndromes. This form of status epilepticus disappears during the waking state and during REM sleep. Cases with hypsarrhythmia without clinical signs may also be classified under the group of electrical or bioelectrical status. In some cases, a continuous hypsarrhythmia is observed only during sleep. In this context, one must also mention those patients who demonstrate continuous activation of spikes, or spike and wave potentials (without clinical seizures) during eye closure.

Adult↗

[Myositis ossificans circumscripta following unusual brain injury].

The case reported here demonstrates the need to consider myositis ossificans after acute injury to the CNS, irrespective of the nature of the trauma. This latter by no means needs to be direct trauma--as the present case shows. When the condition does occur, the time needed for rehabilitation may be significantly lengthened.

Adult↗

[Drug treatment of epilepsy].

The presently preferred anticonvulsives in adults are carbamazepine and valproate. Before the age of 10 years valproate is a second-choice drug only, on account of its hepatotoxicity in patients of this age. Alternatives in generalized primary grand mal seizures are phenobarbital, possible also valproate and phenytoin; in petit mal seizures ethosuximide. At present, numerous substances are being tested for their suitability as anticonvulsives. Those at the most advanced stage of clinical testing are: gabapentine, lamotrigine, oxcarbazepine, progabide, vigabatrin. Among the adverse reactions, the hepatotoxicity of valproate is particularly topical, making comprehensive laboratory examinations mandatory; however, these tests have little prognostic value. During pregnancy the seizure frequency may change. In most patients, the blood levels of the anticonvulsives decrease, despite constant dosage. In the newborn vitamin K1 prophylaxis is mandatory to prevent bleeding. The use of anticonvulsives does not contraindicate nursing.

Anticonvulsants↗

[Depressive disorder of the epilepsy patient--symptoms and factors of influence].

Psychiatric disorders in epilepsy are frequently encountered. Contradictory reports are given in literature about the phenomenology of such disturbances and their relationship to seizure frequency. Depression has been described as mostly like "endogenous" with a family history of psychiatric illness or mostly "reactive". 32 patients with idiopathic Grand mal-seizures were studied using the Inpatient Multidimensional Psychiatric Scale (IMPS). They showed significant higher levels in scales of anxious depression and impaired functioning, no signs of hostility or delusion. Severity of depression was moderate compared with groups of inpatients suffering from endogenous and neurotic-depressive disorders. It was correlated with frequency of epileptic seizures and history of behaviour disturbances in infancy (Spearman-rang correlation).

Adjustment Disorders↗

[Connective tissue changes during longterm anticonvulsive therapy].

Among the connective tissue changes induced by the chronic use of anticonvulsants, gingival hyperplasia associated with the use of phenytoin is the most reliably proven. In addition it is probable that phenytoin can also lead to a coarsening of the facies. Phenobarbital can probably trigger the development of Dupuytren's contracture, polyfibromatosis and/or Sudeck's syndrome. In connection with, or independently of this, phenobarbital can also lead to painful joints. A number of anticonvulsants are suspected of being able to trigger lupus erythematodes.

Anticonvulsants↗

[Neurologic and psychologic disorders in folic acid deficiency].

Folic acid deficiency is the most common of all vitamin deficiencies in North America and in Western Europe, usually in association with other vitamin deficiencies. Alcoholism is considered to be the most frequent cause of folic acid deficiency, as far as the Western world is concerned. Severe neurological and mental disturbances can develop in case of folate deficiency probably long before the manifestation of macrocythaemia. Among the neurological sequelae of folic acid deficiency the main phenomena that are discussed as likely are polyneuropathy, funicular disease of the spine and restless legs. The psychic or mental symptoms that can be ascribed to folic acid deficiency are non-specific and correspond with the symptoms of a psychosis that can have physical causes. Administration of folic acid has repeatedly resulted in significant improvements of neurological and mental symptoms in folic acid deficiency. The exact mechanisms involved in a damage to the nervous system are not sufficiently clarified for folic acid deficiency. Diagnosis is effected mainly by determining the folic acid concentration in the serum. Daily administration of approx. 1.25-15 mg folic acid (oral and/or parenteral) is recommended. Mild side effects such as tiredness and irritability have been noted only with high folic acid dosage levels.

Folic Acid Deficiency↗

[Osteopathia antiepileptica in adolescents and adults].

Since Schmid (115) and Kruse (74) reported on osteopathies occurring after antiepileptic treatment in children, there have been numerous publications concerning the influence of antiepileptics on mineral metabolism in the bones. The investigators' results range from slight anomalies of the plasma levels of calcium, phosphate, alkaline phosphatase, parathormone and 25-hydroxycholecalciferol to severe bone alterations. In the majority of cases, the severe pictures occurred in retarded, neurologically abnormal, institutionalised children who were treated with a high-dose combination of several antiepileptics for epilepsy which was difficult to treat. The first case reports from adults were published by Dent et al. (26). These patients had also been treated since their early youth with an antiepileptic combination. They displayed fractures and suffered from bone pain and muscular weakness. The good response of the rachitic bone alterations to vitamin D treatment both in children and in adults indicated vitamin D deficiency. These reports prompted systematic investigations on the influence of antiepileptics on bone metabolism in numerous hospitals and outpatient departments. According to the available literature, it can be stated that antiepileptic therapy can lead to shifts in calcium and phosphate metabolism and to a raised activity of serum alkaline phosphatase. In studies comprising control groups, the patient treated with anticonvulsants more frequently displayed variations of clinical laboratory parameters. The frequent observation of vitamin D hypovitaminosis led to the assumption that alterations in vitamin D metabolism by enzyme induction are the cause of the disorders in calcium and vitamin D metabolism. This hypothesis was frequently contradicted in recent years after hypocalcaemia and alterations in the mineral content of the bone after antiepileptic therapy had been reported irrespective of the vitamin D level. Besides a restricted intestinal calcium absorption, an influence of antiepileptics on the hormones regulating calcium and phosphate metabolism was found. Thus, a multifactorial genesis of the disorders in bone mineral balance must be assumed. The fact that the vast majority of outpatients with long-term anticonvulsant therapy do not display any disorders of bone metabolism indicate that there are individually different compensation capabilities (possibly of genetic origin). According to the literature, the probability that adults will develop osteomalacia under antiepileptic therapy is associated with the joint presence of various risk factors.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

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.

Adolescent↗

Chronic trichinosis. Clinical, bioptic, serological and electromyographic observations.

Acute trichinosis can be followed by a chronic stage. Myalgia is the main clinical symptom in the chronic course of the disease. From 19 patients with a history of acute trichinosis 2-42 years ago, 15 patients suffered from chronic myalgia. Other typical complaints of our patients in the chronic stage were opthalmodynia, burning of the eyes, headache and early fatigability.

Adult↗

Investigations on the intraindividual constancy of the ratio of carbamazepine to carbamazepine-10,11-epoxide in man.

The constancy of the ratio of carbamazepine (5H-dibenzo[b,f]azepine-5-carboxamide) to carbamazepine-10,11-epoxide was investigated in epileptic patients receiving carbamazepine (Tegretal) monotherapy. We observed a significant interindividual difference, but not between the times in a single patient. Together with the similarly evaluated concordance coefficient, this indicates a certain intraindividual constancy of the ratio between carbamazepine and its epoxide. The carbamazepine:carbamazepine epoxide ratio was dose-dependent, while a sex difference could not be demonstrated.

Adolescent↗

[Acute trichinosis. 193 cases in an epidemic].

In 1982, an epidemic of acute trichinosis occurred in Bitburg with 402 cases. The acute stage was observed and documented in 193 patients. The first signs of the disease appeared on average 17 days after eating trichina-containing meat. Muscle pain was reported by 85% of patients, lid and/or facial edema by 83%, gastrointestinal complaints by 62%, fever by 60%, flu-like symptoms by 56%, headache by 26%, eye complaints by 19%. Eosinophils were present in the blood of 92%. Trichinella antibodies were demonstrated in 98% of patients examined for them. Interstitial myositis was found in 90% of muscle biopsies (from 162 patients). Serious complications--thrombosis, myocarditis, pneumonia, hepatitis or meningism--occurred in 26 (13.5%) of the 193 patients. Even six months after onset of the disease 43% of patients were still not free of symptoms.

Acute Disease↗

[Suicide in epileptic patients].

Suicide and attempted suicide occur with above-average frequency in patients with epilepsy. The proportion of suicide in the overall mortality of epilepsy patients is about 8% and thus about four times more frequent than in the general population. Affective disorders may be contemporaneous with epileptic attacks, or they may occur interictally. The affective disorders leading to suicide may be caused reactively, pharmacogenically, or by the epileptic function disorder itself or by an underlying cerebral disease. For prophylaxis of suicide, it is especially important to be informed about pharmacogenic depressive moods, which evidently occur above all in phenobarbital treatment. Rapid help is often possible by change of medication. Otherwise, the rules of therapy in epilepsy patients in danger of suicide correspond to those of crisis intervention in suicidal individuals in general.

Epilepsy↗

Influence of anticonvulsants and flunarizine on the metabolism of thyroid hormones: speculation about the possible role of calmodulin.

Interference of anticonvulsants with the metabolism of hormones may lead to side effects. Anticonvulsants influence the hypothalamic-pituitary-thyroid axis, in that lowering of thyrotropin [thyroid-stimulating hormone (TSH)] and thyroxine levels is observed. In the present study, flunarizine, a calcium ion blocker, administered as add-on medication, further lowered serum thyroxine but not TSH. The underlying biochemical principle may be an interference with the mediation of signals by calcium-calmodulin at the level of the thyroid follicle.

Adult↗