Biomedical subjects

W O Renier

Publications and source records attributed to W O Renier.

At least 19 recordsLinked to original sources

PubMed2005

Diagnostic reference frames for seizures: A validation study.

INTRODUCTION: We developed structured descriptions of signs and symptoms for specific seizure types (called Diagnostic Reference Frames-DRFs-by us) that can serve as a frame of reference in the process of classifying patients with epileptic seizures. In this study the validity of the DRFs for clinical use is evaluated and described. MATERIAL AND METHODS: In this study we use a decision support system based on the DRFs and using Bayes's rule for the validation of the DRFs. Patient's manifestations are entered in the decision support system and by successively applying Bayes's rule posterior probabilities are calculated. The DRFs with the highest posterior probability gives an indication of the classification of the seizure. The validation of the DRFs was performed by comparing the seizure type with the highest posterior probability with the classification of experienced epileptologists on a series of test cases with known epileptic seizures. In this way we assessed the accuracy of the DRFs in classifying patients with epileptic seizures. RESULTS: We included sixty-six patients in this efficacy study. The patients and/or their relatives described the manifestations occurring during a seizure. Sixty cases (91%) were correctly classified using the decision support system. DISCUSSION: The accuracy of 91 % indicates that the knowledge encoded in the DRFs for the included seizure types is valid. The next step is to test the DRFs in a clinical setting to evaluate the applicability in daily practice.

Adolescent↗

PubMed2005

Cost-effectiveness of add-on lamotrigine therapy in clinical practice.

OBJECTIVE: This retrospective study addresses the cost-effectiveness of add-on therapy with lamotrigine in clinical practice. METHODS: Two years' observational data of 165 patients were used. Seizure frequency, adverse effects and direct medical costs were recorded for the year before and the year after the start of lamotrigine add-on therapy. Therapy effectiveness was measured by: (1) reduction in seizure frequency and (2) retention time. The incremental cost-effectiveness ratio expressed the direct medical cost per patient treated effectively with lamotrigine. RESULTS: The cost of medication was 492 (95% CI: 399-583) higher after the start of lamotrigine therapy. The extra cost of lamotrigine therapy (622) was partly offset by a reduction of the cost of co-medication (-130; 95% CI: -210 to -50). Overall, the total medical cost was 453 higher in the first year of lamotrigine therapy than in the year before the start of lamotrigine. Lamotrigine was effective in 47% of all the patients, making the resultant incremental cost-effectiveness ratio 954 per year. DISCUSSION: Add-on therapy of lamotrigine for patients with uncontrolled epilepsy offers improved health outcomes. Lamotrigine therapy is associated with increased cost (453) and an annual incremental cost-effectiveness ratio of 954. These data, together with utility data published in the literature, support the notion that lamotrigine should be considered as an add-on therapy in for patients with refractory epilepsy.

Adult↗

PubMed2005

Epidemiology of pyridoxine dependent seizures in the Netherlands.

BACKGROUND: Pyridoxine dependent epilepsy is a rare cause of seizures in childhood. The diagnosis is made on clinical criteria, that in many cases are never met. Therefore, epidemiological data on pyridoxine dependency are scarce. AIMS: To study the epidemiology of pyridoxine dependent epilepsy in the Netherlands, and to determine whether the diagnosis is based on the appropriate criteria. METHODS: Nationwide all departments of paediatrics (n = 113) and of paediatric or neonatal neurology (n = 17) were asked to report cases of pyridoxine dependent seizures. Birth incidences were calculated using national data on live births from 1991 to 2003. RESULTS: Response was received from 67% of paediatric departments, including all university hospitals and 94% of child neurology departments. Thirteen patients were reported. Four definite (31%), three probable (23%), and four possible cases (31%) were identified. Two cases (15%) did not meet criteria for either of these groups. The birth incidence was 1:396,000 for definite and probable cases and 1:252,000 when possible cases are included. CONCLUSIONS: Thus far, epidemiological data on pyridoxine dependent seizures were only available from the UK and Ireland. A higher incidence was found in the Netherlands, in accordance with earlier suggestions of a regional difference. The study shows that the diagnosis is often made without performance of a formal trial of withdrawal. The importance of confirming the diagnosis, concerning the consequences as for individual prognosis, the potential side effects of prolonged pyridoxine substitution, and the possibility of treating the mother in case of future pregnancies are emphasised.

Epilepsy↗

PubMed2005

[Epileptic seizures during childbirth in a patient with idiopathic generalised epilepsy].

During her first pregnancy, a 37-year-old woman with idiopathic generalised epilepsy that was adequately controlled with lamotrigine experienced a series of epileptic seizures following an elective caesarean section. The attacks were terminated with diazepam. The following day, she developed EEG-confirmed status epilepticus, for which midazolam was administered intravenously. No further attacks were observed and the patient was later discharged in good condition with a healthy newborn son. She remained on lamotrigine therapy. At the end of her second pregnancy, the patient again experienced tonic-clonic seizures. The dosage of lamotrigine was increased and the patient received clonazepam intravenously, but a new seizure quickly occurred. Following an emergency caesarean section with midazolam treatment, a healthy daughter was born. No further attacks were observed. This case history illustrates the occurrence of adult idiopathic generalised epilepsy and highlights the problems that can arise late in pregnancy and during childbirth.

Adult↗

PubMed2005

Recruitment of a cohort of lamotrigine users through community pharmacists: differences between patients who gave informed consent and those who did not.

OBJECTIVE: Community pharmacists may function as intermediaries in the recruitment of a population-based cohort of patients using specific drugs. In this study, baseline characteristics and the retention rate of patients that gave informed consent, refused and did not answer were compared. METHODS: A total of 1819 patients using the new antiepileptic drug (AED) lamotrigine were asked to provide informed consent for a retrospective chart study via their individual pharmacist. Four possible reactions resulted from the consent question: active consent, active refusal, passive refusal and non-informed. Patient characteristics and lamotrigine retention rate of the different groups were compared. RESULTS: Pharmacists did not inform a total of 183 patients (10%). Of the remaining patients, a total of 968 (59%) gave consent; 101 (6%) actively refused and 567 (35%) did not respond. Age, burden of illness, psychotropic co-medication and continuation of lamotrigine therapy were related to active consent. Lamotrigine retention rate in patients that gave consent was higher than in other patients. CONCLUSIONS: Patient recruitment with community pharmacists as intermediaries for observational studies on the effects of (new) drugs is feasible, and allows access to a broad population of patients. The recruitment procedure, however, may lead to selection bias.

Adolescent↗

PubMed2005

Effectiveness of lamotrigine in clinical practice: results of a retrospective population-based study.

OBJECTIVE: Evaluation of the effectiveness of lamotrigine in a population-based cohort of epilepsy patients. METHODS: Medical charts of 360 patients treated in 37 centres in The Netherlands were reviewed. Effectiveness of lamotrigine therapy was assessed during the first year of use, with patients serving as their own controls. Effectiveness was measured by reduction in seizure frequency and retention time. RESULTS: Effectiveness could only be assessed in 165 patients; assessment in remaining patients was not possible due to various reasons, such as insufficient medical chart information. Lamotrigine was effective in 40% of patients who had been prescribed lamotrigine because of insufficient seizure control (n=112), and 14% of these 112 patients became seizure free. Duration of epilepsy, baseline seizure frequency, valproate use, drug load and number of antiepileptic drugs (AED) used were related to effectiveness of lamotrigine. In this group, 36% continued lamotrigine (LTG) throughout the first year without experiencing a >50% seizure reduction. Lamotrigine was effective in 63% of patients who received the drug because of poor tolerability of other antiepileptic drugs (n=53). DISCUSSION: Lamotrigine is an effective drug in clinical practice. Use of retention time measures only may not correctly reflect the efficacy of antiepileptic drugs.

Adult↗

PubMed2005

Vagus nerve stimulation in patients with catastrophic childhood epilepsy, a 2-year follow-up study.

PURPOSE: To establish the long-term efficacy and tolerability of vagus nerve stimulation (VNS) in children with a Lennox-like syndrome. METHOD: This study was a longitudinal observational prospective cohort analysis. Baseline: 6 months. FOLLOW-UP: 24 months. Screening (baseline and every 6 months): MRI (baseline only), EEG, neuropsychological evaluation, ECG and blood sampling for antiepileptic drug levels. Nineteen children are included. RESULTS: A seizure frequency reduction of 20.6% was found at the end of the follow-up period. No relationship was detected between the length of the stimulation period and the reduction in the seizure frequency. 21% of the patients showed a reduction in seizure frequency of 50% or more. The seizure severity showed improvement in the first 12 months of treatment. The largest seizure reduction was found in the patients with highest frequency of background activity at the baseline EEG. Neuropsychological findings: no negative impact on behaviour, moderate improvement in function, behaviour and mood. Largest seizure reduction was found in the group with the highest baseline mental function. The scores for mental age improved independently of the seizure control. Twelve patients (63%) experienced minor side effects, which subsided after 1 month. CONCLUSION: (1) There was a significant reduction in seizure frequency and severity. (2) No serious side effects were recorded. (3) No negative effects on cognition or quality of life were apparent. (4) Patients with highest baseline mental functioning showed the highest seizure reduction. (5) Those patients with less disturbed EEG (high background activity and less interictal epileptic activity) showed the highest seizure reduction.

Adolescent↗

PubMed2005

Cognitive deterioration and electrical status epilepticus during slow sleep.

The results of long-term follow-up of 10 children with global or specific cognitive deterioration and, on the electroencephalogram, electrical status epilepticus during sleep (ESES) are described. They were referred because of cognitive deterioration and underwent repeated neurological and neuropsychological examinations and all-night electroencephalography. A previous cognitive level was known or could be estimated in all. Seven children had a continuous spikes and waves during sleep (CSWS) syndrome, with global cognitive deterioration in four and more specific cognitive decline in three, and another three children had Landau-Kleffner syndrome (LKS). Of the last three, two children never had seizures, while the other had localization-related epilepsy. No children experienced aggravation of clinical seizures. However, therapy was disappointing. Cognitive dysfunction did not respond to valproate and/or benzodiazepines in 9 of the 10 children. A frontal epileptic focus was found in 5 of 7 children with CSWS, and a left temporal focus in 2 of 3 children with LKS. The ESES persisted in CSWS for 5-9 years and in LKS for 1-5 years, and disappeared at puberty. Good cognitive recovery after disappearance of ESES occurred in only one child, and partial recovery in four. An unfavorable prognosis of cognitive deterioration seems to be related to long-duration ESES and/or early onset epileptic activity. The authors are of the opinion that cognitive deterioration in children, with or without manifest epileptic seizures, should mandate electroencephalographic investigation during sleep.

Adolescent↗

PubMed2005

Severe early onset osteopenia and osteoporosis caused by antiepileptic drugs.

We describe two adult patients with epilepsy who received long-term antiepileptic drug therapy, a woman aged 39 years and a man aged 38 years, in whom severe osteopenia and osteoporosis, respectively, were diagnosed. Both had had epilepsy since childhood, both were seizure free and off medication for several years before the epilepsy started again. The female patient first sustained a complicated pelvis fracture after minor trauma. Next, both patients had infractions of several thoracic vertebrae after a generalised tonic-clonic seizure. Dual-energy X-ray absorptiometry for measurement of the bone mineral density revealed osteopenia in both. Bone biopsy was only performed in the male patient and showed moderate osteoporosis. Taking into consideration the young age for osteopenia and osteoporosis and the absence of other underlying causes, the long-term anticonvulsant therapy is the most likely cause of the development of osteopenia and osteoporosis in these patients. Reviewing recent literature data, advice from healthcare organisations and medical guidelines, the authors were surprised by the lack of protocols and preventive measures for patients with epilepsy who have been on antiepileptic drug therapy for many years. With this article we stress the urgent need to develop protocols and guidelines for preventive interventions.

Absorptiometry, Photon↗

PubMed2004

Diffusion of the new antiepileptic drug lamotrigine in Dutch clinical practice.

INTRODUCTION: Lamotrigine is one of the recently introduced antiepileptic drugs (AEDs) licensed in the Netherlands in 1995. The objective of this study was to examine the diffusion of lamotrigine into clinical practice. Three different aspects of this diffusion process were examined: incidence of use, patient characteristics and changes in prescription patterns in the first 5 years following its introduction. METHODS: A retrospective follow-up study has been conducted using drug prescription data from the database of the Dutch Drug Information Project (GIP database). Patients were included who started with lamotrigine, carbamazepine, phenytoin or valproate in the period between January 1996 and December 2000. Incidence of use was calculated for the four drugs. Multiple logistic regression analysis was used to determine differences in baseline characteristics. The Chi-square test was used to analyse changes in the usage patterns of lamotrigine. RESULTS: The study population consisted of a total of 29,718 patients who were prescribed carbamazepine, phenytoin, valproate or lamotrigine for the first time in the study period. Carbamazepine and valproate accounted for the majority of all new prescriptions; the incidence of lamotrigine use remained stable with 4.4 patients per 100,000 per year. Baseline characteristics of lamotrigine differed depending on the patient's age and gender (OR 3.7, 95% CI 3.3-4.2; OR 1.4, 95% CI 1.3-1.5) relative to the conventional AEDs. In a large majority of cases, lamotrigine was used as a second-line or third-line AED. Physicians prescribing lamotrigine were predominantly neurologists, in contrast to prescribers of conventional AEDs. The prevalence of psychotropic medication and migraine-abortive drugs was significantly lower in users of lamotrigine than in users of conventional AEDs. During follow-up, several significant trends were noticed in the prescribing of lamotrigine with regard to age groups, gender, antiepileptic history and off-label use. DISCUSSION: Lamotrigine is prescribed to a population different from that using conventional AEDs. The uptake of lamotrigine in clinical practice is slow, for reasons probably related to characteristics of the drug itself and the prescribers. During the observation period, lamotrigine diffused gradually towards more first-line use as an AED and more off-label use.

Adolescent↗

PubMed2004

Patterns of lamotrigine use in daily clinical practice during the first 5 years after introduction in the Netherlands.

OBJECTIVE: Follow-up data on the long-term effectiveness (efficacy and tolerability) of lamotrigine are limited. A useful though crude measure for effectiveness in daily clinical practice is the treatment retention rate determined from drug dispensing data. This study describes the baseline characteristics, the usage patterns and the retention rate of this antiepileptic drug (AED) in a population-based cohort of lamotrigine users in the Netherlands during the first 5 years after its registration in 1995. Data from this cohort are compared with those from the initial randomized clinical trials (RCTs) in patients with refractory epilepsy. METHODS: This retrospective cohort study used dispensing data from community pharmacies. Baseline characteristics and usage patterns were evaluated for first time users of lamotrigine in this study. Usage patterns were characterized as continued, add-on or discontinued use during the patient observation time window. Cox regression analysis was used to explore possible relationships between baseline characteristics and specific usage patterns defined. The baseline characteristics and discontinuation rates in this cohort study were compared with RCT data reported in medical literature. RESULTS: A total of 3598 lamotrigine users were identified. The mean age of the population was 39 years and 54% were female. On average, patients used two other AEDs at the start of lamotrigine therapy and approximately 6% of the patients had no history of prior AED use. The discontinuation rate was 25% after 1 year, and approximately 32% at the end of the 5-year study. Addition of another drug or discontinuation was seen in more than half of the population 3 years after the start of therapy. Concurrent use of valproic acid was associated with a better retention rate. Absence of AED history, use of antidepressants, or use of migraine abortive drugs resulted in an increased likelihood of discontinuing lamotrigine. The population from RCTs differed from the study cohort with respect to age, concurrent use of AEDs and length of follow-up. CONCLUSION: Data from RCTs cannot easily be extrapolated to daily clinical practice. In this large, observational study, lamotrigine therapy failed in a considerable number of patients, although the mean retention rate was better than previously reported by others. Population-based linkage of health care records can be used to further clarify the effectiveness of lamotrigine.

Adolescent↗

PubMed2004

An approach to knowledge base construction based on expert opinions.

OBJECTIVES: To describe, validate and demonstrate an approach for knowledge base construction based on expert opinions. METHODS: A knowledge base containing the frequency of occurrence of manifestations in epileptic seizures is constructed based on information provided by neurologists/epileptologists. The reliability of the responses is determined with the inter-rater intraclass correlation coefficient (ICC). If the ICC is not large enough the Spearman-Brown prophecy formula can be used to predict the number of additional experts. We propose a method to assess whether an additional expert provides information consistent with the already acquired data as well as a method to detect experts with deviating opinions. The power of the first method was determined. RESULTS: Data were collected for five seizure types. The ICCs determined from the responses for the various seizure types after inclusion of the additional experts was in all cases almost equal to 0.9, the target value. Yet one expert with diverging opinions concerning the frequency of occurrence of manifestations for different seizure types could be identified. Excluding this participant improved the reliability of the data. The power of the methods was good (> or =0.75). CONCLUSIONS: It is shown that human experts can provide reliable information about the frequency of occurrence of manifestations in epileptic seizures. In addition, the described approach correctly identified neurologists/epileptologists with both consistent and diverging opinions about the frequency of occurrence of manifestations in a number of seizure types.

Artificial Intelligence↗

PubMed2003

[Toxic epidermal necrolysis due to lamotrigine].

A 10-year-old girl developed a progressive rash and high fever more than a month after the start of lamotrigine as add-on medication for therapy-resistant epilepsy. A skin biopsy indicated toxic epidermal necrolysis (Lyell syndrome). Because her situation deteriorated and the lesions of the skin and mucosa progressed, she was transferred to a specialised centre for burn patients. Despite maximal supportive treatment, she died 3 weeks after the first skin lesions. Even with a low initial dosage of lamotrigine followed by a slow increase, a fatal toxic epidermal necrolysis is still possible. This should be kept in mind, especially in case of concurrent administration of valproic acid.

Anticonvulsants↗

PubMed2003

Development and developmental disorders of the human cerebellum.

The human cerebellum develops over a long time, extending from the early embryonic period until the first postnatal years. This protracted development makes the cerebellum vulnerable to a broad spectrum of developmental disorders. The development of the cerebellum occurs in four basic steps: 1) characterization of the cerebellar territory at the midbrain-hindbrain boundary; 2) formation of two compartments for cell proliferation: first, the Purkinje cells and the deep cerebellar nuclei arise from the ventricular zone of the metencephalic alar plate; second, granule cell precursors are formed from a second compartment of proliferation, i. e. the upper rhombic lip; 3) inward migration of the granule cells: granule precursor cells form the external granular layer, from which (and continuing into the first postnatal year), granule cells migrate inwards to their definite position in the internal granular layer, and 4) formation of cerebellar circuitry and further differentiation. The precerebellar nuclei, i. e. the pontine nuclei and the inferior olive, arise from the lower rhombic lip. Developmental disorders of the cerebellum are often accompanied by malformations of the precerebellar nuclei. In this review the development of the cerebellum and some of its more frequent developmental disorders, such as the Dandy-Walker and related midline malformations, and the pontocerebellar hypoplasias, are discussed.

Cerebellar Diseases↗

PubMed2003

Development of diagnostic reference frames for seizures. Part 1: inter-participant agreement in the selection of symptoms.

OBJECTIVE: Our aim is to develop reliable descriptions of various seizure types, which will be used as a basis for decision support. We use expert opinions in this process. In this contribution we evaluate the inter-participant agreement in the selection of frequently occurring symptoms for the description of seizure types. METHOD: We compared the actual agreement among participants with the agreement that would result from random symptom selection as well as with the maximal agreement attainable. For each seizure type we calculated the reliability coefficients of the responses. RESULTS: For all seizure types we found that the agreement in symptom selection among the participants is significantly higher than expected by chance, but not reaching the maximum agreement attainable. The reliability coefficients varied between 0.56 and 0.74 for the various seizure types. CONCLUSION: Although the participants do not reach the maximum agreement attainable in the selection of symptoms, the majority agreement on characteristic frequently occurring symptoms for the different seizure types does approach the maximum agreement attainable. Therefore, we conclude that expert opinions can be used for building descriptions of seizure types. However, to derive a reliable set of symptoms for the construction of the diagnostic reference frames (DRFs) more participants are needed.

Decision Making, Computer-Assisted↗

PubMed2003

Development of diagnostic reference frames for seizures. Part 2: are seizure descriptions discriminative?

OBJECTIVE: To determine whether the seizure descriptions given by a group of neurologists/epileptologists are discriminative. METHOD: We constructed templates for various seizure types describing how often symptoms were selected by the participants. We defined a matching score to indicate the match between such a template and the symptoms selected by each neurologist/epileptologist individually and computed the scores for each of the sets of selected symptoms with all templates. Correlation coefficients were calculated between the templates. RESULTS: Data were collected from 24 participants. The matching scores and the correlation coefficients both show that participants provide discriminative descriptions of the seizure types. Descriptions of aggregated seizure types, such as primary generalized seizures, are less discriminatory than the descriptions of more specific seizure types. CONCLUSION: We concluded that the participants in our study selected symptoms that result in discriminative descriptions of the seizure types. This indicates that knowledge elicitation by using the opinions of a group of clinical experts is possible. The study also indicates that the design of the study could be ameliorated in several ways. These findings will be taken into account when designing the final study.

Decision Making, Computer-Assisted↗

PubMed2003

Selection criteria for the clinical use of the newer antiepileptic drugs.

In recent years, several new antiepileptic drugs (AEDs) have been licensed: felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide. These drugs have proven efficacy as add-on therapy in patients with difficult-to-treat partial epilepsy, as 20-50% of patients treated in add-on trials experienced a seizure reduction of >or=50%. Relatively few trials have been conducted to evaluate these drugs as monotherapy for patients with newly diagnosed epilepsy. In the monotherapy trials that have been conducted, the newer drugs were often as efficacious as conventional drugs, and their tolerability was often better. However, the methodology of these trials can be criticised. Because of the relative lack of robust data for the newer agents, the conventional drugs have thus far maintained their status as first-line monotherapy. However, when first-line monotherapy fails, an alternative drug has to be chosen from the available conventional and newer drugs. This article aims to give detailed background information on the newer AEDs in order to enable physicians to make a rational choice from the available drugs for individual patients. Data are provided for the different newer AEDs on mechanisms of action; efficacy in refractory partial epilepsy, newly diagnosed epilepsy in adults and generalised seizure types; adverse effects; pharmacokinetics; and use in special patient categories.

Animals↗

PubMed2003

How many neurologists/epileptologists are needed to provide reliable descriptions of seizure types?

We are developing seizure descriptions as a basis for decision support. Based on an existing dataset we used the Spearman-Brown prophecy formula to estimate how many neurologist/epileptologists are needed to obtain reliable seizure descriptions (rho = 0.9). By extending the number of participants to the required level we found that the number of participants needed to obtain a reliability coefficient of 0.9 were in accordance with the number of participants determined from the Spearman-Brown prophecy formula. Systematic differences between the participants were minor and not statistically significant.

Clinical Competence↗