Biomedical subjects
H Meinardi
Publications and source records attributed to H Meinardi.
The influence of subclinical epileptiform EEG discharges on driving behaviour.
EEG and driving behaviour were monitored in 6 patients with subclinical focal and generalised epileptiform EEG discharges during 420 km of actual motorway driving in a suitably instrumented vehicle. Evidence of impaired driving performance during subclinical discharges was significant in 3 subjects (P less than 0.025 or less than 0.05) and was suggestive (P less than 0.1) in 1. The two patients with greatest impairment had active epilepsy, whereas the others had been seizure-free for upwards of 4 years. No other features appeared to be predictive of altered driving behaviour during discharges.
Seven day administration of lamotrigine in epilepsy: placebo-controlled add-on trial.
A double-blind placebo-controlled trial of 7 days administration of lamotrigine as add-on therapy was performed in 10 patients with frequent therapy-resistant, chiefly partial, seizures. Dosage was adjusted on the basis of estimated half-life. Six patients showed a 50% seizure reduction on lamotrigine and two an increase. Side effects (ataxia, dizziness and apathy) occurred in 3 patients, but only at blood levels above 3 micrograms/ml, and were rapidly relieved when the dose was reduced in two. EEG spike counts were significantly reduced on lamotrigine. There was no evidence of interactions with co-medication.
Photosensitive patients: symptoms and signs during intermittent photic stimulation and their relation to seizures in daily life.
Thirty six patients were studied with a classical photoparoxysmal EEG response to intermittent photic stimulation (IPS). Clinical observations and complaints reported by patients during standardised IPS were recorded and compared with historical data. Twenty seven patients experienced impaired consciousness or showed motor phenomena such as involuntary opening of the eyes or jerking on one or both sides of the body. Twenty five patients had sensations such as pain in the eyes, jerking etc. There existed no relation between the duration of the evoked discharges (0.5-3 seconds) and observed signs or complaints. In 11 instances the clinical features found during IPS were not reported in a history taken from the patient and relatives.
[Medical information for nurses. Epilepsy and pregnancy].
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Blood donation, a risk for epileptic patients?
Generally patients with epilepsy will not be accepted as blood donors by blood banks. A survey in the Dutch blood banks revealed two blood banks with a total of 13 donors suffering from epilepsy. We also questioned the Chapters of the International League against Epilepsy. The answers on a national and international level differed widely. We believe that the rare convulsion during blood donation is not an epileptic seizure, but in fact an emotive syncope. We advocate the acceptance of patients with epilepsy, free of seizures for 2 years irrespective of their medication, as blood donors.
Assessment of effects of antiepileptic drugs.
Pharmacological studies form an important adjunct to epilepsy monitoring and conversely long-term EEG and video recording are of value for assessing antiepileptic drug (AED) effects. Clinical estimates of the incidence of brief frequent seizures as absences is often difficult but greater reliability can be achieved by long-term monitoring of the seizures themselves or of the associated EEG discharges. There are, however, very marked spontaneous short-term fluctuations in discharge rates and the amounts of ictal epileptiform activity in short conventional EEGs rarely provide any useful index of AED action. Acute investigations are of value for assessing new AEDs or experimental methods of administration and for pharmacokinetic studies. For this purpose either spontaneous EEG discharges or photosensitivity may provide quantitative measures of antiepileptic effect. Long-term AED monitoring by means of an indwelling catheter indicates the time course of blood drug levels to be more complex and variable than might be expected from simple pharmacokinetic models. Short-term fluctuations in AED concentrations have little effect on epileptiform EEG activity or seizure control but are often responsible for intermittent side-effects. Conversely diagnostic EEG and monitoring studies may be required to classify seizures as an aid to determining appropriate medication and may explain apparent resistance to therapy, due to pseudo-seizures, reflex or self-induced epilepsy. Finally a case is presented for combined pharmacological EEG and video-monitoring in the preliminary assessment of new AEDs in order to improve the design of subsequent clinical trials.
[Use of valproic acid in pregnancy: an indication for prenatal diagnosis of spina bifida].
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Spina bifida and in-utero exposure to valproate.
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Temporal characteristics of seizures and epileptiform discharges.
The time relations of epileptic events have been studied in 3 sets of data: (I) counts of individual epileptiform discharges in twelve 48 h EEG recordings, (IIa) seizure calendars of 30 therapy-resistant outpatients participating in a drug trial, (IIb) seizure calendars of 10 mentally subnormal epileptic patients resident in a long-stay unit. The EEG data I were characterized most often by a Poisson distribution of intervals between discharges and the occurrence of marked periodicities, particularly at night. The periods of rhythmic nocturnal events ranged from 13 to 142 min and did not appear to correspond to the REM/non-REM cycle. In the seizure data IIa and b a Poisson distribution of intervals between events was found in half the patients. Periodicities occurred only in group IIa and did not correspond to weekly or monthly cycles. A stochastic process is considered to be the model which best fits these data.
Teratogenicity of antiepileptic drug combinations with special emphasis on epoxidation (of carbamazepine).
A higher rate of congenital anomalies has been found after prenatal exposure to some combinations of antiepileptic drugs than to the separate drugs. In an earlier study a rate of 58% congenital anomalies was found among infants exposed to carbamazepine plus phenobarbitone plus valproate. In this study an attempt was made to determine whether this specific combination of drugs has teratogenic activity due to metabolic interaction. The epidemiological data were analyzed further. The high rate of congenital anomalies after prenatal exposure to this combination could not be explained by the effects of one or two of these drugs only, nor by additional exposure to phenytoin. Assuming that metabolic interaction in the arene oxide pathway resulting in accumulation of epoxide intermediates of antiepileptic drugs could be responsible for teratogenesis, the ratio of carbamazepine to carbamazepine-10, 11-epoxide concentrations in serum was determined in adult patients with epilepsy who were treated with carbamazepine only and with different combinations of phenobarbitone, valproate, and/or phenytoin. For carbamazepine monotherapy the mean ratio was 8.19. For all combinations lower ratios were found, indicating accumulation of carbamazepine-10,11-epoxide. The combination of carbamazepine, phenobarbitone, valproate, and phenytoin showed the lowest ratio (1.94), followed by carbamazepine, valproate, and phenytoin and by carbamazepine, phenobarbitone, and valproate (2.81 and 3.18, respectively). These results give rise to the question of whether the combination of carbamazepine, phenobarbitone, valproate, and/or phenytoin has teratogenic activity by accumulation of carbamazepine-10,11-epoxide or other epoxide intermediates, and stress the need to take metabolic interactions into account when investigating the teratogenic activity of antiepileptic drugs.
Double-blind placebo-controlled trial of flunarizine as add-on therapy in epilepsy.
In a therapy-resistant epileptic population with partial complex seizures with or without secondary generalization, addition of flunarizine to existing therapy was accompanied by a significant reduction in complex partial and tonic-clonic seizures. This result did not appear to be due to serial effects or changes in the plasma levels of the co-medication. Side effects were rare. The serum flunarizine levels (13.8 ng/ml; range, 3-32.5 ng/ml) were lower than previously reported on a daily dose of 10 mg. This may reflect increased metabolism due to induction of liver enzymes by the co-medication. Given this finding, together with the low incidence of side effects, a further study is required to determine whether higher blood levels would give an improved degree and incidence of seizure reduction.
Carbamazepine and serum sodium levels.
Serum sodium levels of 674 epileptic patients were tabulated according to the following categories: less than 135 mmol/L, hyponatremia (28 patients); 135-145 mmol/L, normonatremia (530 patients); greater than 145 mmol/L, hypernatremia (116 patients). One hundred one patients were treated with antiepileptics without carbamazepine (CBZ), 113 with CBZ monotherapy, and 460 with CBZ plus other antiepileptic drugs. Twenty-three patients could be followed up after the first detection of a serum sodium level of less than 135 mg/L. Ten patients were consistently hyponatremic (greater than 50% of the follow-up measurements were less than 135 mg/L), whereas the remaining 13 were occasionally hyponatremic. The following facts could be derived from the study: (1) The hyponatremic group was significantly older compared with the other groups. (2) In patients not treated with CBZ, no hyponatremia was seen. Only two patients on CBZ monotherapy showed hyponatremia. (3) The combination of CBZ, valproic acid, especially in high dosages, and barbiturates seemed to lead to hyponatremia. (4) The excretion of antidiuretic hormone, measured in 12 patients, was subnormal (less than 25 ng/24 h) in seven hyponatremic patients and in three normonatremic patients and normal (25-250 ng/24 h) in two other normonatremic patients. (5) Cyclic AMP, measured in five hyponatremic patients, was normal. (6) In all patients the hyponatremia was slight and did not cause any clinical symptoms. Special treatment was not required.
[Relations to the use of antiepileptics by the pregnant woman to the development of congenital abnormalities in her child].
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Valproate-ethosuximide combination therapy for refractory absence seizures.
Five patients had absence seizures refractory to treatment with either ethosuximide or valproate sodium. To determine their response to combination therapy with the two drugs, four of the five had serial 24-hour intensive monitoring studies that included cable telemetric EEG recording, closed-circuit television observation, and frequent antiepileptic drug (AED) serum level determinations. The resultant data confirmed the clinical and EEG effects of serial alterations in AED programs. All five became seizure free with combination therapy. Combination therapy with ethosuximide and valproate should be considered in patients whose absence seizures do not respond to standard therapeutic measures.
Developments in pharmacotherapy of epilepsy.
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False-negative pregnancy test women taking carbamazepine.
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[Clinical evaluation of EEG telemetry and videomonitoring in 212 patients with epilepsy].
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