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Biomedical subjects

P Boon

Publications and source records attributed to P Boon.

At least 19 recordsLinked to original sources

Opinion of Belgian neurologists on antiepileptic drugs: Belgian Study on Epilepsy Treatment (BESET).

OBJECTIVES: To describe the choice of treatment in adult patients with epilepsy in Belgium, to detect the presence or absence of consensus among neurologists in epilepsy treatment, and to analyze the gaps between current guidelines and prescriptions. MATERIALS AND METHODS: Hundred Belgian neurologists were systematically interviewed between May and June 2003 using a structured questionnaire (modified Rand method). RESULTS: Initial monotherapy was the preferred treatment strategy. Valproate was the first choice in idiopathic generalized epilepsy (IGE) and carbamazepine in focal epilepsy (FE). The new antiepileptic drugs (AED) were usually recommended in second-line. However, in special treatment situations, they were considered first-line, e.g., lamotrigine in case of women of childbearing age. CONCLUSIONS: Neurologists reached consensus for most questions on epilepsy treatment. In 2003, monotherapy with valproate and carbamazepine was the common treatment strategy in Belgium, whereas lamotrigine and to a lesser extent levetiracetam, topiramate, and oxcarbazepine were predominantly prescribed in second-line. This is in agreement with the recently published UK epilepsy guidelines but not in agreement, however, with the US guidelines, that for new onset epilepsy, new and old drugs are equally effective. Belgian neurologists, except for some special situations still prefer old drugs as first line.

Adult↗

Vagus nerve stimulation does not affect spatial memory in fast rats, but has both anti-convulsive and pro-convulsive effects on amygdala-kindled seizures.

Vagus nerve stimulation (VNS) is an adjunctive treatment for refractory epilepsy. Using a seizure-prone Fast-kindling rat strain with known comorbid behavioral features, we investigated the effects of VNS on spatial memory, epileptogenesis, kindled seizures and body weight. Electrodes were implanted in both amygdalae and around the left vagus nerve of 17 rats. Following recovery, rats were tested in the Morris water-maze utilizing a fixed platform paradigm. The VNS group received 2 h of stimulation prior to entering the Morris water-maze. Rats were then tested in the kindling paradigm wherein the VNS group received 2 h of stimulation prior to daily kindling stimulation. Finally, the abortive effects of acute VNS against kindling-induced seizures were determined in fully kindled rats by applying VNS immediately after the kindling pulse. Body weight, water consumption and food intake were measured throughout. Memory performance in the Morris water-maze was not different between control and vagus nerve stimulation rats. Similarly, kindling rate was unaffected by antecedent VNS. However, pro-convulsive effects (P<0.05) were noted, when VNS was administered prior to the kindling pulse in fully kindled rats. Yet, paradoxically, VNS showed anti-convulsant effects (P<0.01) in those rats when applied immediately after the kindling stimulus. Body weight was significantly lower throughout kindling (P<0.01) in VNS-treated rats compared with controls, which was associated with reduced food intake (P<0.05), but without difference in water consumption. VNS appears to be devoid of significant cognitive side effects in the Morris water-maze in Fast rats. Although VNS exhibited no prophylactic effect on epileptogenesis or seizure severity when applied prior to the kindling stimulus, it showed significant anti-convulsant effects in fully kindled rats when applied after seizure initiation. Lastly, VNS prevented the weight gain associated with kindling through reduced food intake.

Amygdala↗

Memory performance during the intracarotid amobarbital procedure and neuropsychological assessment in medial temporal lobe epilepsy: the limits of material specificity.

We investigated the relationship between material-specific memory performance elicited during the Wada test, or intracarotid amobarbital procedure (IAP), and classic neuropsychological assessment in 89 surgical candidates with refractory medial temporal lobe epilepsy (MTLE). The neuropsychological battery included measures of simple and complex verbal and visual memory, whereas the IAP material consisted of verbal and dually encodable stimuli. Neuropsychological testing revealed that reduced verbal memory performance was associated with left-sided MTLE, whereas visual memory tasks revealed no differences between patients with left-sided and right-sided MTLE. During IAP, memory performance was worse with the ipsilesional hemisphere, regardless of lesion side. Most importantly, performance on verbal memory tests was significantly, but moderately, correlated with left hemispheric IAP performance, indicating that memory tasks using verbal material are a valid marker of left hemispheric integrity in left language-dominant MTLE patients and significantly predict left hemispheric memory performance during IAP. In contrast, performance on classic visual memory tests is unrelated to right hemispheric IAP performance, suggesting that the currently used visual memory stimuli do not reflect right hemispheric sensitivity.

Adult↗

EFNS guideline on the management of status epilepticus.

The objective of the current paper was to review the literature and discuss the degree of evidence for various treatment strategies for status epilepticus (SE) in adults. We searched MEDLINE and EMBASE for relevant literature from 1966 to January 2005. Furthermore, the Cochrane Central Register of Controlled Trials (CENTRAL) was sought. Recommendations are based on this literature and on our judgement of the relevance of the references to the subject. Recommendations were reached by informative consensus approach. Where there was a lack of evidence but consensus was clear we have stated our opinion as good practice points. The preferred treatment pathway for generalised convulsive status epilepticus (GCSE) is intravenous (i.v.) administration of 4 mg of lorazepam or 10 mg of diazepam directly followed by 15-18 mg/kg of phenytoin or equivalent fosphenytoin. If seizures continue for more than 10 min after first injection another 4 mg of lorazepam or 10 mg of diazepam is recommended. Refractory GCSE is treated by anaesthetic doses of midazolam, propofol or barbiturates; the anaesthetics are titrated against an electroencephalogram burst suppression pattern for at least 24 h. The initial therapy of non-convulsive SE depends on the type and the cause. In most cases of absence SE, a small i.v. dose of lorazepam or diazepam will terminate the attack. Complex partial SE is initially treated such as GCSE, however, when refractory further non-anaesthetising substances should be given instead of anaesthetics. In subtle SE i.v. anaesthesia is required.

Anticonvulsants↗

Clinical relevance of memory performance during Wada is stimulus type dependent.

OBJECTIVES: This study aimed to investigate whether different types of memory stimulus provide different information during the Wada or intracarotid amytal procedure (IAP) in patients with refractory medial temporal lobe epilepsy (MTLE). METHODS: Eighty nine surgical candidates with documented MTLE and selected for left hemispheric language dominance underwent memory assessment with verbal and dually encodable stimuli during a presurgical IAP. RESULTS: The overall IAP memory performance with the left hemisphere is significantly better than with the right hemisphere regardless of lesion side. This can be explained by the left hemispheric advantage of encoding all stimuli, whereas the right hemisphere has only limited resources to encode verbal stimuli. More importantly, it appeared that dually encodable items remain more readily recognised following injection ipsilateral to the lesion, whereas verbal items are always better recognised following right hemisphere injection regardless of lesion side. CONCLUSIONS: Verbal IAP stimuli show left hemispheric sensitivity in left language dominant MTLE patients. The dually encodable items of the IAP appear lesion sensitive.

Adult↗

Subacute Hashimoto's encephalopathy, treated with plasmapheresis.

We report a patient with subacute diffuse encephalopathy characterised by rapidly progressive dementia with visual hallucinations, myoclonus and generalised seizures. She was euthyroid but showed high serum levels of thyreoglobulin and thyreoperoxidase antibodies. Hashimoto's encephalopathy was diagnosed. MRI of the brain in the acute phase demonstrated no structural abnormalities. However in the mesotemporal regions and the anterior parts of the brain, a decrease of the N-acetylaspartate and an increase of the Choline-containing compounds was found on MRI-spectroscopy. Reversal of these abnormalities was demonstrated a few months later after starting therapy. Plasmapheresis resulted in normalisation of serum levels of the antibodies and rapid clinical improvement. This observation supports the idea that a correlation exists between the serum levels of the thyroid auto-antibodies and the course of the clinical illness.

Female↗

Detection of spike and wave discharges in the cortical EEG of genetic absence epilepsy rats from Strasbourg.

Genetic absence epilepsy rats from Strasbourg (GAERS) are a strain of Wistar rats in which all animals present spontaneous occurrence of spike and wave discharges (SWD) in the cortical electroencephalogram (EEG). In this paper, we present a method for the detection of SWD, based on the key observation that SWD are quasi-periodic signals. A spectral-comb based analysis method is used to extract the fundamental frequency and the percentage of energy explained by the harmonic spectral components is subsequently used as a detection parameter. It is shown that a maximum sensitivity and specificity of up to 96 per cent can be achieved. We also compared the performance of this method with the methods presented in the literature and conclude that the surplus value of the novel detection method lies in the higher specificity that can be obtained in the analysis of long-term EEG fragments, which are contaminated by artefacts and contain large portions of slow-wave sleep.

Action Potentials↗

Magnetic source imaging contributes to the presurgical identification of sensorimotor cortex in patients with frontal lobe epilepsy.

OBJECTIVE: One of the primary goals of preoperative evaluation of patients considered to be candidates for epilepsy surgery is the delineation of eloquent cortex adjacent to the area of resection. The aim of this study is the functional localization of the sensorimotor cortex in relation to an epileptogenic frontal lobe lesion, thus enabling a more complete resection in these patients while minimizing the risk of postoperative neurological deficits. METHODS: Participating in this study were patients with epilepsy, diagnosed as being related to a left or right frontal lobe lesion. Magnetoencephalographic responses evoked by electrical stimulation of the left and right hand median nerve were localized using single time-point equivalent dipole (ED) modeling, taking into account the realistic shape of the head. Instead of relying on the primary component (N/P 20) of the somatosensory evoked magnetic fields (SEFs) in this study ED fits were obtained for each time-point of the somatosensory evoked responses. On a cortical rendering, the reconstructed dipoles were depicted relative to the anatomy obtained from 3D-magnetic resonance imaging. RESULTS: The results of single time-point ED analysis including all the components of the responses indicated that the sources underlying the SEFs are located at the borders of the central sulcus (CS). The opposite direction of the sources underlying, respectively, the primary and subsequent late component of the SEFs indicated distinct sources located at the opposite banks of the CS. These sources, therefore, might correspond to the sensory hand projection area and the primary motor area of the sensorimotor cortex. It appeared that the location of the EDs obtained for the SEFs of 4 of the 7 patients studied were asymmetric for the left and right hemisphere, probably because of a displacement of the sensorimotor areas relative to the CS. The systematic assessment of the dipole fits compared to brain anatomy confirmed that volume conduction changes due to the lesion were not responsible for these observed deviations, thus leaving as explanation space-occupying and neurophysiological changes due to the lesion.

Adolescent↗

Usefulness of language and memory testing during intracarotid amobarbital testing: observations from an fMRI study.

BACKGROUND: Several procedures for testing language lateralization and memory function exist during the intracarotid amobarbital test (IAT). The use of functional magnetic resonance imaging (fMRI) gives the opportunity to assess the validity of some of these procedures, or at least to inspect the neuronal correlates. A comprehensive fMRI protocol was tested, aimed at addressing aspects of lateralization of language, as well as testing memory in relation to activation of mesiotemporal regions. Here we report observations with possible consequences for the current IAT procedures. MATERIALS AND METHODS: The protocol consisted of three language tasks (overt naming, semantic decision and silent word generation) and two memory tasks (encoding and retrieving visual scenes). The paradigms used a block-related procedure in nine right-handed normal volunteers. During the procedure dynamic weighted full brain images were acquired which are sensitive to the blood oxygenation activation effect. RESULTS: Encoding showed symmetrical bilateral activation in the mesiotemporal regions, specifically the hippocampus, parahippocampal gyrus and fusiform gyrus. With a retrieval task activation of the mesiotemporal areas was restricted to the posterior hippocampal area. Overt object naming showed results, similar to encoding tasks with bilateral activation of hippocampal areas. Silent word generation showed much stronger ability to lateralize than the other two language-related tasks and especially object naming. CONCLUSION: Activation revealed by fMRI activation shows that IAT procedures, using active semantic language processing or comprehensive procedures with multiple language tasks have the highest guarantee for individual activation lateralization. Simple object naming does not guarantee a lateralized language fMRI activation pattern. Of the different memory procedures during IAT, the procedures (Interview and the Montreal) demanding encoding processing will be related to larger areas of bilateral hippocampal activation than procedures (Seattle) exclusively requiring retrieval. Moreover, tasks using recognition of previously presented language items (naming objects) are equally effective for assessing hippocampal activation compared with presenting separate memory items.

Adult↗

The pathophysiology of motor symptoms in Parkinson's disease.

This review focuses on some of the known and hypothetical pathophysiological mechanisms underlying the motor symptoms in Parkinson's disease (PD). Current views on these mechanisms have largely been influenced by models of basal ganglia functioning and dysfunctioning. These models have allowed to explain some clinical findings and to predict a number of results of basal ganglia surgery in movement disorders. However, neurophysiological studies as well as neurochemical data have broadened our vision on basal ganglia functioning and dysfunctioning in PD. Moreover, these more fundamental insights in basal ganglia functioning allow new concepts on the development of treatment strategies, and on the prevention of motor fluctuations in PD.

Basal Ganglia↗

Developing a comprehensive presurgical functional MRI protocol for patients with intractable temporal lobe epilepsy: a pilot study.

Our aim was to put together and test a comprehensive functional MRI (fMRI) protocol which could compete with the intracarotid amytal (IAT) or Wada test for the localisation of language and memory function in patients with intractable temporal lobe epilepsy. The protocol was designed to be performed in under 1 h on a standard 1.5 tesla imager. We used five paradigms to test nine healthy right-handed subjects: complex scene-encoding, picture-naming, reading, word-generation and semantic-decision tasks. The combination of these tasks generated two activation maps related to memory in the mesial temporal lobes, and three language-related maps of activation in a major part of the known language network. The functional maps from the encoding and naming tasks showed typical and symmetrical posterior mesial temporal lobe activation related to memory in all subjects. Only four of nine subjects also showed symmetrical anterior hippocampal activation. Language lateralisation was best with the word generation and reading paradigms and proved possible in all subjects. The reading paradigm enables localisation of language function in the left anterior temporal pole and middle temporal gyrus, areas typically resected during epilepsy surgery. The combined results of this comprehensive f MRI protocol are adequate for a comparative study with the IAT in patients with epilepsy being assessed for surgery.

Adult↗

Vagus nerve stimulation for epilepsy, clinical efficacy of programmed and magnet stimulation.

RATIONALE: Vagus nerve stimulation (VNS) by intermittent and programmed electrical stimulation of the left vagus nerve in the neck, has become widely available. It is an effective treatment for patients with refractory epilepsy. Patients can be provided with a magnet that allows to deliver additional stimulation trains. Since earlier studies have demonstrated the persistence of a stimulation effect after discontinuation of the stimulation train, we evaluated the clinical efficacy of VNS both in the programmed intermittent stimulation mode and magnet stimulation mode. METHODS: A group of 30 patients (16 F, 14 M) with medically refractory partial epilepsy, who were unsuitable candidates for resective surgery, were included in the study. The patients, their companions and caregivers were instructed on how to administer additional stimulation trains using a hand-held magnet when an aura or a seizure onset occurred. Patients or caregivers could recognize habitual seizures and were able to evaluate sudden interruption of these seizures. Using seizure diaries, detailed accounts of magnet use and regular clinic follow-up visits, data on seizure frequency and severity and number of magnet applications were collected. Patients who provided unreliable information were excluded from the analysis. RESULTS: Forty-seven percent of all patients had an improvement in seizure control with a reduction in seizure frequency of more than 50% during a mean follow-up of 33 months (range: 4-67 months). More than half of the patients used the magnet and provided reliable information. In 63% of patients who were able to self-administer or receive additional magnet stimulation, seizures could be interrupted, be it consistently or occasionally. More than half of the patients who reported a positive effect of magnet stimulation became responders. In most cases the magnet was applied by a caregiver. CONCLUSIONS: To our knowledge, this study is the first to explore the efficacy of magnet-induced vagus nerve stimulation. Results suggest that the magnet is a useful tool that provides patients and mainly caregivers with an additional means of controlling refractory seizures. Additional controlled studies comparing programmed stimulation and magnet-induced stimulation in monitoring conditions are warranted.

Adolescent↗

Dose-response effect of levetiracetam 1000 and 2000 mg/day in partial epilepsy.

PURPOSE: To evaluate the efficacy, dose-response, tolerability, and withdrawal effects of levetiracetam (Keppra) as adjunctive therapy in adult patients with partial epilepsy. METHODS: In this European multicenter, double-blind, randomized, cross-over trial, levetiracetam 1000 or 2000 mg/day given in two divided doses was compared to placebo as add-on therapy in 324 patients with refractory partial seizures with or without secondary generalization. This trial consisted of six periods: an 8- or 12-week baseline, a treatment period A (4-week titration and 12-week evaluation), a treatment period B (4-week titration and 12-week evaluation), and a withdrawal period. During each evaluation period (A and B), patients received two of the three possible treatment regimens. RESULTS: This study provides additional information on dose-response effects and withdrawal phenomena and confirms the responder and seizure freedom rates previously reported in the parallel part of the study (Epilepsia 41 (2000) 1179-1186). Both doses of levetiracetam significantly decreased mean partial seizure frequency compared with placebo (P<0.001), and significantly more patients receiving levetiracetam had > or = 50 and > or = 75% reductions in partial seizure frequency (1000 mg, P=0.004 and P=0.043, respectively; 2000 mg P=0.001 and P<0.001, respectively). In addition, 5.5% (10/183) of patients receiving levetiracetam 1000 mg/day and 6.3% (11/175) of patients receiving levetiracetam 2000 mg/day were seizure-free during the corresponding evaluation period, compared with 1.2% (2/172) of patients on placebo. A within-patient comparison revealed a significantly greater responder rate for the higher levetiracetam dose (P=0.018). The most commonly reported adverse effects (> or = 5% and more frequent in one of the groups with levetiracetam) were headache, asthenia, infection, somnolence, pharyngitis, dizziness, and pain. No withdrawal-related adverse events were reported during the cross-titration period. CONCLUSIONS: Levetiracetam was effective and well-tolerated and decreased seizure frequency in a dose-dependent manner, with no evidence of typical withdrawal-related adverse events or rebound phenomena after withdrawal or down-titration.

Adolescent↗

Direct medical costs of refractory epilepsy incurred by three different treatment modalities: a prospective assessment.

PURPOSE: More than 20% of epilepsy patients have refractory seizures. Treatment options for these patients include continued polytherapy with/without novel antiepileptic drugs (AEDs), epilepsy surgery (ES), or vagus nerve stimulation (VNS). The purpose of this study was prospectively to compare epilepsy-related direct medical costs (ERDMCs) incurred by these different treatment modalities. METHODS: Eighty-four patients underwent a complete presurgical evaluation protocol at our institution. As a result, 24 (29%) patients were treated with continued AED polytherapy only; 35 (40%) underwent ES; and 25 (30%) had VNS. In each patient, annual costs in the 2 years preceding the therapeutic decision (ERDMC-pre) and during the follow-up afterward (ERDMC-post) were prospectively calculated. Furthermore, frequency of complex partial seizures with/without secondary generalization (CPS+/-SG), dosage and number of AEDs, number of hospital admission days, clinic visits, and laboratory tests before and after the therapeutic decision also were prospectively assessed. ERDMC-pre and ERDMC-post were compared in and among the three treatment groups. RESULTS: In patients conservatively treated with AEDs, mean frequency of CPSs decreased from 12 per month to nine per month, whereas mean ERDMCs decreased from $2,525 U.S. to $2,421 U.S. In surgical patients, mean seizure frequency decreased from six to fewer than one per month; mean ERDMCs per year decreased from $1,465 U.S. preoperatively to $1,186 U.S. postoperatively. In the VNS group, mean seizure frequency decreased from 21 per month to seven per month. ERDMCs in this subgroup decreased from $4,826 U.S. to $2,496 U.S. Mean seizure frequency changes were significant when conservatively treated patients were compared with surgically treated and VNS patient groups (chi2 test, p<0.001 and p=0.0019, respectively). ERDMC changes in conservatively treated patients also were statistically significant when compared with surgically treated and VNS patients (chi2 test, p=0.0007 and p=0.0036, respectively). No statistically significant differences were found in ERDMC changes between the surgical and VNS groups (chi2 test, p=0.387). CONCLUSIONS: Ongoing daily treatment of patients who underwent resective surgery costs significantly less than conservative treatment. For patients in whom resective surgery is not an option, ERDMC show a significant decrease in VNS-treated patients compared with conservatively treated patients.

Adult↗