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H Meinardi

Publications and source records attributed to H Meinardi.

At least 37 records · Page 2Linked to original sources
PubMed1997

Vascular determinants of epilepsy: the Rotterdam Study.

PURPOSE: To investigate the relation between vascular determinants and epilepsy in an elderly population. METHODS: This is a cross-sectional, community-based, case-control study. The total study population was comprised of 4,944 subjects, 65 of whom had epilepsy which conformed to International League Against Epilepsy (ILAE) criteria. Vascular determinants that were evaluated included a history of stroke or myocardial infarction, peripheral vascular disease, hypertension, serum total cholesterol and left ventricular hypertrophy. Multivariate logistic regression analysis was used to calculate prevalence odds ratios (OR), adjusted for age and gender, as a measure of the strength of the associations. RESULTS: A history of stroke was strongly associated with lifetime epilepsy (OR 3.3; 95% CI [Confidence Interval] 1.3-8.5), as well as with late-onset epilepsy (OR 3.1; 95% CI 0.9-10.6). All vascular determinants were associated with lifetime epilepsy and late-onset epilepsy, with odds ratios >1. When stroke patients were excluded, the odds ratios were statistically significant for the relationships between total cholesterol and late-onset epilepsy (OR 1.3, 95% CI 1.0-1.6) and left ventricular hypertrophy and late-onset epilepsy (OR 2.9, 95% CI 1.0-8.6). Furthermore, presence of any of these vascular indicators was twice as common among subjects with late-onset epilepsy as compared with subjects without epilepsy (OR 2.0, 95% CI 0.9-4.2), and this was statistically significant when stroke patients were excluded (OR 2.1, 95% CI 1.0-4.7). CONCLUSIONS: These results suggest that there may be a relationship between vascular factors and the risk of late-onset epilepsy, apart from the relationship that exists through clinically overt stroke.

Age Factors↗
PubMed1997

Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy.

PURPOSE: To quantify the risks of intrauterine antiepileptic drug (AED) exposure in monotherapy and polytherapy. METHODS: Data from five prospective European studies totaling 1,379 children were pooled and reanalyzed. Data were available for 1,221 children exposed to AED during pregnancy and for 158 children of unexposed control pregnancies. RESULTS: Overall, when comparing a subgroup of 192 children exposed to AED with 158 children of matched nonepileptic controls, there was an increased risk of major congenital malformations (MCA) in children exposed to AED during gestation [relative risk (RR) 2.3; 95% confidence interval (CI): 1.2-4.7]. A significant increase in risk was found for children exposed to valproate (VPA) (RR 4.9; 95% CI: 1.6-15.0) or carbamazepine (CBZ) (RR 4.9; 95% CI: 1.3-18.0) in monotherapy. When comparing different AED regimens during all 1,221 pregnancies, risks of MCA were significantly increased for the combination of phenobarbital (PB) and ethosuximide (RR 9.8; 95% CI: 1.4-67.3) and the combination of phenytoin, PB, CBZ, and VPA (RR 11.0; 95% CI: 2.1-57.6). Offspring of mothers using > 1,000 mg VPA/day were at a significantly increased risk of MCA, especially neural tube defects, compared to offspring exposed < or =600 mg VPA/day (RR 6.8; 95% CI: 1.4-32.7). No difference in risk of MCA was found between the offspring exposed to 601-1,000 mg/day and < or =600 mg/day. CONCLUSIONS: This reanalysis shows that VPA is consistently associated with an increased risk of MCA in babies born to mothers with epilepsy. Significant associations were also observed with CBZ. Larger prospective population-based studies are needed to evaluate the risks of many other less frequently prescribed treatment regimens, including newly marketed AEDs.

Abnormalities, Drug-Induced↗
PubMed1997

Adverse effects in epilepsy therapy. Wait and see or go for it?

OBJECTIVES: Attention for adverse effects (AEs) is important for optimizing epilepsy treatment. However, a uniform strategy is lacking. In particular there appears to be a dichotomy between those who "wait and see" and those who "go for it", i.e. routinely check a list of AEs. Our intention is to identify the effects of different approaches. METHODS: Trial reports on carbamazepine or valproate monotherapy (Medline-search), and data from the Nijmegen Epilepsy Research Group were analyzed. RESULTS: Analysis suggests that for certain AEs, such as diplopia, dysarthria, affect and mood disturbances, headache, dizziness, gastro-intestinal disturbances, dermatological disturbances and idiosyncratic reactions, it does not matter which approach is chosen. However, sedation, cognitive impairments, sexual dysfunction, hair changes, nystagmus, gait disturbances, tremor and weight changes are reported more frequently when routinely checked. The value of routine laboratory monitoring is, however, questioned. CONCLUSIONS: Use of different strategies to detect AEs obstructs estimation of risks of AEDs. Baseline measurements and regular checking for those AEs, which are reported more frequently by authors who actively search for AEs, is advisable.

Anticonvulsants↗
PubMed1997

Newer anticonvulsant drugs: role of pharmacology, drug interactions and adverse reactions in drug choice.

In the last few years a number of new anticonvulsants have been introduced into clinical practice mainly as add-on therapy in patients who do not become seizure-free while receiving established anticonvulsants. Up to now, no single drug has been shown to be more effective at controlling seizures of a particular type than another, so other factors such as mechanism of action, pharmacokinetics, dosage regimens or the spectrum of adverse drug reactions and interactions are used when making a choice between one agent and another. The mechanism of action of tiagabine and vigabatrin is very specific; both agents increase gamma-aminobutyric acid (GABA) levels through inhibition of reuptake and catabolism respectively. However, the mechanism of action of gabapentin is unknown and those of felbamate, lamotrigine and topiramate are not sufficiently clarified as yet, and may be multiple. Great advances have been made in improving the pharmacokinetic characteristics of these newer anticonvulsants. Gabapentin and vigabatrin exhibit relatively ideal pharmacokinetic properties as they are not bound to proteins, are excreted mostly unchanged in the urine and show linear pharmacokinetics. Lamotrigine possesses a highly variable elimination half-life depending on the co-medication. Tiagabine is highly protein bound and zonisamide shows nonlinear pharmacokinetics; both these drugs are extensively metabolised. Problematic drug interactions between newer anticonvulsants and other drugs in general occur rarely when these agents are given concomitantly. However, in common with most new drugs, there are very few data on the use of the newer anticonvulsants in women of childbearing age. Studies done so far on interactions with oral contraceptives used low anticonvulsant dosages for a very short time. The newer anticonvulsants elicit adverse reactions that, while not being unique, are particularly associated with that drug. For example, felbamate may cause aplastic anaemia and fulminant liver failure, lamotrigine is prone to cause skin rash, and oxcarbazepine may cause symptomatic hyponatraemia. Topiramate and zonisamide cause kidney stones, and vigabatrin may induce psychiatric syndromes. Although highly diverse in structure and activity, these newer drugs offer new possibilities for treating refractory epilepsy. However, since no single factor can dictate the choice of drug nor predict the success of treatment, prescribing of these rather expensive drugs has to depend upon careful consideration of the aims of treatment, the characteristics of the drug and the needs of the individual patient.

Adult↗
PubMed1996

Status epilepticus in children.

Aetiology and outcome of status epilepticus in children are different in comparison with adult patients. The main characteristics of status epilepticus in 112 children (age 6 months-15 years) are presented, with special attention to age, duration of status epilepticus, causes, medical complications and therapy. The greater part of these children was known to have had prior epilepsy, a considerable number with mental retardation. Outcome in convulsive status epilepticus is influenced by cause, duration, age, the occurrence of medical complications and quality of treatment. Outcome in nonconvulsive status epilepticus is good and does not seem to be influenced by the treatment strategy. The use of a therapy protocol may prevent unnecessary delay and contribute to a better outcome.

Adolescent↗
PubMed1996

Prevalence of epilepsy in the elderly: the Rotterdam Study.

We assessed the prevalence of epilepsy in an elderly population in The Netherlands. The study was conducted from 1991 to 1993 as part of the Rotterdam Study, a population-based door-to-door study of all elderly people living in Ommoord, a suburb of Rotterdam, and included 5,559 persons aged 55-95 years. All subjects were screened for epilepsy through direct questions regarding the existence of epilepsy and antiepileptic drug (AED) use, in addition to relevant questions from the World Health Organization (WHO) protocol for epidemiologic studies of neurologic diseases. Further evaluation of screen positives was made by a panel of 1 study physician and 4 epileptologists, who also classified all confirmed cases of epilepsy according to the classifications of the International League Against Epilepsy (ILAE). The overall prevalence of active epilepsy in our study population was 0.9% including special syndromes and 0.8% excluding special syndromes. The prevalence increased with age from 0.7% for those aged 55-64 years to 1.2% for those aged 85-94 years. The increase with age was detected among men and women both. Our study confirms other findings showing that the prevalence of active epilepsy increases with age in the elderly. The prevalence figures in our study were high as compared with those of other population-based studies. Epilepsy appears to be a major cause of morbidity in the elderly.

Age Distribution↗
PubMed1996

Simple partial status epilepticus: causes, treatment, and outcome in 47 patients.

A retrospective case note review was conducted of 47 patients of 15 years and older who had sustained simple partial status epilepticus (SPSE) in The Netherlands between 1980 and 1987. In 46 patients the type of SPSE was somatomotor (in four adversive), and in one aphasic with visual and auditory hallucinations. SPSE was more common over the age of 50. Six of 27 patients with previous epilepsy had an acute symptomatic cause. In 20 patients without previous epilepsy stroke was the most frequent cause (75%). Outcome was determined by the underlying cause. In one patient the continuing epileptic activity may have caused neuronal damage.

Adult↗
PubMed1996

Non-convulsive status epilepticus: causes, treatment, and outcome in 65 patients.

The incidence of non-convulsive status epilepticus (NCSE) in The Netherlands is not known. Files of admissions in the years 1980-7 were studied from 40 adult patients (older than 15 years) with complex partial status epilepticus (CPSE) and 25 with absence status epilepticus (ASE). The clinical presentation sometimes made distinction between CPSE and ASE possible. Focal clinical signs were more frequent in CPSE; a fluctuating level of consciousness was more often present in ASE. All patients, but one, with ASE and most patients with CPSE (28) were known to have had previous epilepsy. Outcome in ASE was good in all. Outcome in CPSE depended on the underlying cause and quality of treatment. In three patients inadequate treatment probably contributed to morbidity.

Adolescent↗
PubMed1996

Use of antiepileptic drugs in a community-dwelling Dutch population.

We compared the treatment policy for patients with epilepsy in six Dutch cities, comprising 302, 149 inhabitants, with the treatment policies of a secondary referral center (a university hospital) and tertiary referral centers (outpatient departments of epilepsy centers). By comparing the prevalence of individuals receiving antiepileptic drugs in the six cities with the epidemiologic data for epilepsy in Rochester, Minnesota, we concluded that prescription data offer a suitable means by which to estimate the prevalence of epilepsy in a community. To compare prescriptions in cases of polytherapy, we normalized data by using defined daily doses published by the WHO Collaborating Center for Drugs Statistics Methodology and the Nordic Council on Medicines and concluded that the defined daily doses of antiepileptic drugs should be further elaborated. There is a need to obtain complete dose-response curves of equivalent antiepileptic drugs in humans. The trend of drugs use found in the six cities, the university hospital, and the epilepsy centers is, however, in accord with the expectations regarding primary, secondary, and tertiary referral centers.

Adolescent↗
PubMed1995

Neither dosage nor serum levels of antiepileptic drugs are predictive for efficacy and adverse effects.

In order to assess whether doses or serum levels are predictive for the efficacy and adverse effects of antiepileptic drugs (AEDs), measures for exposure to drug combinations have to be used. For doses, the ratio of the observed prescribed daily dose (PDD) and the average defined daily dose (DDD) considered effective for the main indication of the drug was used. In analogy for serum levels, the OSL/ATL ratio, i.e. the ratio of the observed serum level and the average therapeutic level was used. In polypharmacy these ratios can be summed as the are normalized measures of strength. The correlations of these ratios with outcome measures were studied in 200 patients attending out-patient clinics of special centres for epilepsy; half of these patients were treated with monopharmacy and half with polypharmacy. As outcome measures the following indices were used: the index of seizures, which quantifies seizure type and frequency, the seizure activity index, the neurotoxicity score, the systemic toxicity score, and the composite index of impairments, which is the sum of the seizure activity index and the neurotoxicity score and the systemic toxicity score. When all data were pooled, the correlation coefficient between the PDD/DDD ratio and the OSL/ATL ratio was 0.77. However, when the data were examined separately for the monopharmacy and polypharmacy groups, the correlation was 0.31 for the monopharmacy group and 0.50 for the polypharmacy group. Neither the PDD/DDD ratio nor the OSL/ATL ratio correlated with the composite index of impairments or with any of the individual indices. Factors such as the difficulty of titrating the endpoint of seizure suppression and the development of tolerance to adverse drug effects may perhaps be responsible for these findings. This observational study signals the problem.

Adult↗
PubMed1995

Pseudo-epileptic seizures: hypnosis as a diagnostic tool.

In this pilot study hypnosis was used in an attempt to provide evidence of a psychogenic component of pseudo-epileptic seizures. The criterion for psychogenesis was the reversal of the amnesia, which is often present in epileptic- and pseudo-epileptic seizures. The technique has been validated by a semi-blind referral of cases for analysis after the clinician had been able to make a firm diagnosis based on electro-encephalic corroboration of the nature of the seizure. In eight out of nine patients (of the original 13 patients, three patients dropped out and one patient was not evaluable), the experimental diagnosis corresponded with the clinical diagnosis. As pseudo-epileptic seizures can be characterized by their dissociative nature, a reasonable hypothesis is that patients with pseudo-epileptic seizures are more responsive to hypnosis than patients with epileptic seizures. Measurements of hypnotizability among seven patients with epileptic seizures and six patients with pseudo-epileptic seizures supported this supposition.

Adolescent↗
PubMed1995

Monotherapy or polytherapy for epilepsy revisited: a quantitative assessment.

Some investigators argue that treating epilepsy with several antiepileptic drugs (AEDs) simultaneously (polytherapy) may give rise to more adverse effects than monotherapy, but this argument lacks supporting quantitative data. To reexamine this issue, we recruited a cohort of patients from the outpatients of the Special Centres for Epilepsy in The Netherlands and from the outpatients of the Department of Neurology, Nijmegen University, The Netherlands. Two tools were used for analysis. All daily doses of antiepileptic drugs (AEDs) were standardized by the ratio of prescribed daily dose to defined daily dose (PDD/DDD). The DDD is the assumed average effective daily dose for a drug used for its main indication in adults. The assignment of DDD values is the task of the World Health Organization (WHO) Collaborating Centre for Drugs Statistics Methodology and Nordic Council on Medicines, which regularly publishes Guidelines for Defined Daily Doses. The severity of adverse effects (AE) was assessed by using the Neurotoxicity Index and the Systemic Toxicity Index as developed by the VA Cooperative Study Group for their recent studies comparing the efficacy and tolerability of AEDs. One hundred sixty-one patients received monotherapy; all had a PDD/DDD ratio < or = 2/day; 128 of 262 patients receiving polytherapy also had < or = 2 PDD/DDD ratios/day. The mono- and polytherapy groups were stratified according to the PDD/DDD ratio. The prevalence of neurological AE for patients with similar PDD/DDD ratios was 50-80% for monotherapy patients and 50-82% for polytherapy patients. The difference between the mono- and polytherapy groups was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Cerebrospinal fluid examinations in cryptogenic West and Lennox-Gastaut syndrome before and after intravenous immunoglobulin administration.

Before and after administration of intravenous immunoglobulin (IVIg), cerebrospinal fluid (CSF) was examined in a homogeneous group of 15 patients with cryptogenic types of West syndrome (WS) and Lennox-Gastaut syndrome (LGS). The purpose of the present CSF study was: (i) to elucidate possible etiological factors and consequences of these severe forms of epilepsy, and (ii) to elucidate mechanisms of action and adverse effects of IVIg. Hypotheses concerning etiological factors like central nervous system infections, neuroimmunological disorders, or disturbances in neurotransmitter metabolites could not be confirmed. These normal CSF findings are in accordance with the concept of a cryptogenic etiology of the epilepsies in the reported patients. Nor could we confirm hypotheses concerning seizure consequences, such as increased blood-CSF permeability, increased markers of brain cell destruction, or increased metabolic components. Following IVIg administration in these patients, all with an on the whole undisturbed blood-CSF barrier permeability as measured by Q albumin, the CSF IgG concentrations increased significantly and proportionally to the Q albumin level. No signs of adverse effects of IVIg such as aseptic meningoencephalitis were found in 165 infusions of IVIg performed in the 15 children.

Child↗
PubMed1994

Immunoglobulin treatment in epilepsy, a review of the literature.

The purpose of this study is to ascertain possible efficacy and to understand possible mechanisms of action of intramuscular or intravenous immunoglobulin (IVIg) in the treatment of intractable epilepsy, through a review of all identifiable articles on this topic. In 24 studies, none with a placebo controlled design, 368 patients with epilepsy receiving IVIg were identified. Patients' ages ranged from < 1 to 35 years, mean 7.3 years. Female/male ratio was 0.6. All patients were reported to suffer from intractable epilepsy. The average percentage of patients with an IgG2 deficiency was 25%. The total dose of IVIg varied between 0.3 and 6.8 g/kg for a period of 0.15 to 12 months. Whenever reported, adverse effects of IVIg were minimal. None of the studies reported the need of cessation of IVIg administration due to adverse effects. On the average, the mean clinical seizure reduction and the mean EEG improvement were 52% and 45%, respectively. On the average the percentage of patients with complete seizure remission and the percentage of patients with behavioral improvement were 23% and 63%, respectively. Cumulative meta-analysis of the identified articles is not possible due to the lack of controlled studies, the heterogeneity of the available studies, and the possible publication bias of unpublished negative data. Given these pitfalls, this literature study nevertheless allows some conclusions: (i) There is no formal proof of efficacy of IVIg treatment in epilepsy, and the present review underscores the need of controlled clinical trials before firm conclusions concerning efficacy can be drawn. The uncontrolled clinical observations discussed in this 'state-of-the-art' review generate suggestive evidence at best. They suggest that IVIg might be effective in some patients with intractable epilepsy, and may be considered as a safe add-on medication in various types of idiopathic and symptomatic intractable epilepsy. (ii) Review of the literature did not help in explaining intractable epilepsy or the mechanism of action of IVIg, but did permit some inferences that could serve to design future clinical and experimental approaches to IVIg administration in epilepsy.

Adolescent↗
PubMed1994

Survey of 260 epileptic patients treated with oxcarbazepine (Trileptal) on a named-patient basis.

We report the clinical findings on all 260 epileptic in- and out-patients of a Dutch epilepsy centre ever treated with oxcarbazepine on a named-patient basis. All but three patients had been previously treated, in vain, with carbamazepine. Of 260 patients, exposed for 935 patient-years, 161 were still treated on reference date, the longest duration of oxcarbazepine treatment being 119 months. Fourteen patients were lost to follow up. Four successfully stopped treatment after full control of their epilepsy for over three years. Seven stopped because they got worse instead of better. Seventy-three did not benefit sufficiently to continue on OCBZ in view of alternative treatment possibilities. In one patient the final diagnosis was pseudo-seizures. The drug is particular useful in patients who require polypharmacy and patients with adverse effects to carbamazepine.

Adolescent↗
PubMed1994

Epilepsy treatment in The Netherlands. Comparison of matched groups of two medical centres.

To test the feasibility of comparing epilepsy treatment policies and outcome, a secondary and a tertiary epilepsy care facility have been audited in a previous study (1). Marked differences were observed in the treatment policies and outcome and in the distribution of seizure types and duration of epilepsy. For this reason the patients of that study were matched according to seizure type and duration of epilepsy, resulting in two groups each of 32 patients per centre. The outcome of treatment was assessed by using clinimetrical indexes for seizure frequency and severity and toxicity of medication, resulting in the Composite Index of Impairments (CII), reflecting all treatment-related impairments. For the statistical analysis the X2-test and the Kruskal-Wallis test were used. Differences were found to be statistically significant when p < 0.05. No distinct differences were found in the treatment policies of both centres. However, differences were observed in the outcome of treatment. The toxicity ratings in this study were significantly higher for the Epilepsy Centre. Also the Composite Index of Impairments (CII) was significantly higher at the Epilepsy Centre. The number of patients with a CII score of > 100 did not differ significantly for both centres. The finding that pharmacotherapy is similar in both centres, suggests that pharmacotherapy is pushed to its limits in both, and that referral to a tertiary facility is mainly for the non-pharmacotherapeutic care modalities available. For the corroboration of this assumption the use of a quality of life index would be more appropriate than the CII.

Adolescent↗