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Paul Boon

Publications and source records attributed to Paul Boon.

At least 19 recordsLinked to original sources
PubMed2006

Differentiation assays of bone marrow-derived Multipotent Adult Progenitor Cell (MAPC)-like cells towards neural cells cannot depend on morphology and a limited set of neural markers.

There are accumulating studies that report a neurogenic potential of bone marrow-derived cells both in vitro as well as in vivo. Most claims of neural "transdifferentiation" have based their conclusions on morphology and neural gene expression. Recently, doubts have been raised about the validity of both outcome parameters since non-neural cells can extend neurites and show aberrant neural gene expression as a response to stress inducing factors. In this study, we compared bone marrow-derived Multipotent Adult Progenitor Cell (MAPC)-like cells and neural stem cells (NSC) in their morphology and neural gene expression profile after neural differentiation using three differentiation protocols. We evaluated the expression of five neuroglial antigens [neurofilament 200 (NF200); beta III tubulin (beta3 tub); tau; Glial Fibrillary Acidic Protein (GFAP); Myelin Basic Protein (MBP) and RIP antigen] using real-time PCR (RT-PCR) and immunocytochemistry (ICC). MAPC-like cells adopted a neural-like morphology in one protocol but a fibroblast-like morphology in the two other protocols. RT-PCR and ICC show that MAPC-like cells already express the neural antigens beta III tubulin and NF200 at baseline, but no upregulation of these genes after exposure to three distinct differentiation protocols was seen. In contrast, NSC adopt neural and glial morphologies with a clear increase in expression of all neuroglial genes in all differentiation protocols used. In conclusion, our data demonstrate that neural-like morphology and expression of a limited set of neural marker genes by MAPC-like cells after differentiation are not absolute proof of neural transdifferentiation because MAPC-like cells only partially meet the criteria which are fulfilled by NSC after neural differentiation.

Adipogenesis↗
PubMed2006

Vagus nerve stimulation and cognition.

Vagus nerve stimulation (VNS) has been developed as an add-on treatment for patients with refractory epilepsy. Based on the clinical observation of improved cognition in many epilepsy patients who received VNS, we reviewed the recent literature for evidence concerning the cognitive effects of this treatment. From most of these studies it seems that, with currently used stimulation parameters, the effects on memory are only of theoretical importance. However, some animal studies suggest positive effects on specific modalities of memory function. In studies in epilepsy patients, there is no evidence of adverse effects on cognition but clear-cut positive effects cannot be expected either. Preliminary results of VNS in the treatment of diseases associated with cognitive decline such as Alzheimer's disease seem promising but need to be further investigated.

Animals↗
PubMed2006

Dynamics of epileptic phenomena determined from statistics of ictal transitions.

In this paper, we investigate the dynamical scenarios of transitions between normal and paroxysmal state in epilepsy. We assume that some epileptic neural network are bistable i.e., they feature two operational states, ictal and interictal that co-exist. The transitions between these two states may occur according to a Poisson process, a random walk process or as a result of deterministic time-dependent mechanisms. We analyze data from animal models of absence epilepsy, human epilepsies and in vitro models. The distributions of durations of ictal and interictal epochs are fitted with a gamma distribution. On the basis of qualitative features of the fits, we identify the dynamical processes that may have generated the underlying data. The analysis showed that the following hold. 1) The dynamics of ictal epochs differ from those of interictal states. 2) Seizure initiation can be accounted for by a random walk process while seizure termination is often mediated by deterministic mechanisms. 3) In certain cases, the transitions between ictal and interictal states can be modeled by a Poisson process operating in a bistable network. These results imply that exact prediction of seizure occurrence is not possible but termination of an ictal state by appropriate counter stimulation might be feasible.

Adolescent↗
PubMed2006

A novel splicing mutation in KCNQ2 in a multigenerational family with BFNC followed for 25 years.

PURPOSE: A large multigenerational family with benign familial neonatal convulsions (BFNC) was revisited to identify the disease-causing mutation and to assess long-term outcome. METHODS: We supplemented the original data with recent clinical and neurophysiologic data on patients and first-degree relatives, including information on seizure recurrence. We conducted linkage analysis at the EBN1 and EBN2 loci, followed by mutation analysis of KCNQ2. We evaluated the qualitative effect of the KCNQ2 mutation at the messenger RNA (mRNA) level by using reverse-transcribed total RNA isolated from leukocytes. RESULTS: Thirteen relatives had a history of neonatal convulsions, 11 of whom showed remission within 2 months. One patient showed an atypical course of neonatal convulsions, developing photosensitive myoclonic epilepsy at age 13 years. We found suggestive linkage of the BFNC phenotype to the 20q13-EBN1 locus (lod score, 2.03) and an intronic mutation IVS14-6 C>A in KCNQ2 segregating with the trait in all affected members, but absent in 100 unrelated control subjects. This mutation creates a new, preferentially used, splice site. Alternative splicing adds 4 nt containing a premature stop codon to the transcript, resulting in a truncated protein after position R588. CONCLUSIONS: We detected and characterized a novel splicing mutation in the brain-specific KCNQ2 gene by using easily accessible blood leukocytes. Aberrant splicing cosegregates with BFNC but not with photosensitivity.

Adolescent↗
PubMed2006

Levodopa-induced alterations in speech rate in advanced Parkinson's disease.

The effect of speech rate on overall intelligibility in Parkinson's Disease (PD) is still a matter of debate. A comparison of the results of previous studies on speech rate in PD is hampered by methodological differences. In this study, we evaluated the effects of levodopa on speech rate and on its variability in a standardized reading task. Twenty-five patients were studied before and after levodopa administration while reading a standardized text. In accordance with previous studies, no significant improvement of speech rate was found. Rather an increased variability of speech rate in the on-medication state could be demonstrated. It is possible that this increased variability may be the consequence of respiratory deficits due to levodopa-induced dyskinesia or an increase of dysfluencies. However, the effects of defective auditory feedback and disturbed executive function cannot be ruled out.

Antiparkinson Agents↗
PubMed2006

Neuromodulation with levetiracetam and vagus nerve stimulation in experimental animal models of epilepsy.

Epilepsy is a neurological disorder consisting of recurrent seizures, resulting from excessive, uncontrolled electrical activity in the brain. Epilepsy treatment is successful in the majority of the cases; however; still one third of the epilepsy patients are refractory to treatment. Besides the ongoing research on the efficacy of antiepileptic treatments in suppressing seizures (anti-seizure effect), we want to seek for therapies that can lead to plastic, neuromodulatory changes in the epileptic network. Neuropharmacological therapy with levetiracetam (LEV) and vagus nerve stimulation (VNS) are two novel treatments for refractory epilepsy. LEV acts rapidly on seizures in both animal models and humans. In addition, preclinical studies suggest that LEV may have antiepileptogenic and neuroprotective effects, with the potential to slow or arrest disease progression. VNS as well can have an immediate effect on seizures in epilepsy models and patients with, in addition, a cumulative effect after prolonged treatment. Studies in man are hampered by the heterogeneity of patient populations and the difficulty to study therapy-related effects in a systematic way. Therefore, investigation was performed utilizing two rodent models mimicking epilepsy in humans. Genetic absence epilepsy rats from Strasbourg (GAERS) have inborn absence epilepsy and Fast rats have a genetically determined sensitivity for electrical amygdala kindling, which is an excellent model of temporal lobe epilepsy. Our findings support the hypothesis that treatment with LEV and VNS can be considered as neuromodulatory: changes are induced in central nervous system function or organization as a result of influencing and initiating neurophysiological signals.

Animals↗
PubMed2006

Standards of care for non-convulsive status epilepticus: Belgian consensus recommendations.

Non-convulsive status epilepticus (NCSE) makes up around one-third of all cases of SE, affecting approximately 1,000 to 4,000 individuals per year in Belgium. Compared with convulsive SE, NCSE has received considerably less attention, is underdiagnosed and undertreated. However, if recognised, NCSE can however be treated successfully. A workshop was convened by neurologists from major Belgian centres to review the latest information on NCSE and to make recommendations on diagnosis and treatment. These recommendations are not only intended for neurologists, but also for primary care physicians and physicians in intensive care units. NCSE should be suspected whenever cases of fluctuating consciousness or abrupt cognitive or behavioural changes are noted. Confirmation of diagnosis by EEG should be obtained wherever possible. In view of the often subtle clinical signs, EEG is also vital for monitoring treatment outcome. Non-comatose patients should generally be treated in a neurology ward since referral to an ICU is unnecessary. First-line treatment should be an intravenous benzodiazepine. For many patients who fail to respond to benzodiazepines, intravenous valproate will successfully abrogate seizure activity. Intravenous phenytoin can be used in patients with focal NCSE in whom valproate is contraindicated or ineffective. Time and care should be spent in identifying an appropriate and effective antiepileptic drug regimen without recourse to anaesthesia. For comatose patients, treatment intensity should be graded according to epilepsy history, general medical state and prognosis. In some patients, intensive remedial measures may allow rapid resolution of NSCE, whereas in more vulnerable patients, such treatment may be counterproductive.

Algorithms↗
PubMed2005

Deep brain stimulation of the internal pallidum in multiple system atrophy.

We describe the outcome of deep brain stimulation of the internal pallidum in a 57-year old patient with multiple system atrophy. Although the prominent dystonic features of this patient were markedly attenuated post-operatively, the outcome was to be considered unfavourable. There was a severe increase in akinesia resulting in overall decrease of mobility in limbs as well as in the face. As a result, the patient was anarthric and displayed dysphagia. A laterality effect of stimulation on oro-facial movements was demonstrated. The patient died 7 months post-operatively. This report adds to the growing consensus that multiple system atrophy patients are unsuitable candidates for deep brain stimulation.

Deep Brain Stimulation↗
PubMed2005

Rapid kindling in preclinical anti-epileptic drug development: the effect of levetiracetam.

PURPOSE: This study assesses the use of the serial day Rapid Kindling with Recurrent Hippocampal Seizures (RKRHS) model in drug testing by investigating the anti-epileptic effect of levetiracetam (LEV), a novel anti-epileptic drug (AED) with a unique preclinical profile. METHODS: Male Wistar rats (n=16) were implanted with a stimulation/recording electrode unit in the right hippocampus and epidural recording electrodes. One week later, all rats received 12 stimulations each day for several consecutive days according to the serial day RKRHS protocol, until they were fully kindled. Fully kindled rats were then randomly assigned to an active (n=8) and a control (n=6) group and injected once (intraperitoneal, i.p.) with levetiracetam (54 mg/kg) or saline (0.9% NaCl, 2 ml/kg), respectively. One hour later, the rats received additional kindling stimulations, during which the effect of LEV was assessed. RESULTS: One hour following injection of LEV, mean seizure stage dropped to 1.67+/-1.03 compared to 5+/-0 in controls (p<0.05). Mean ADD was also significantly shorter in the active group than in controls; 21.16+/-5.03 s versus 57.24+/-8.16s, respectively (p<0.05). A gradual, time-dependent decline was noted in the anti-epileptic effect of LEV but this effect stayed statistically significant at least up to 2.5 h (p<0.05). CONCLUSION: LEV was demonstrated to have anti-epileptic properties in RKRHS that compared to those in traditional kindling and contrast with results from classical screening tests. RKRHS may represent a valuable and sensitive screening tool early in the drug screening process.

Animals↗
PubMed2005

Small animal positron emission tomography during vagus nerve stimulation in rats: a pilot study.

Vagus nerve stimulation (VNS) is an effective neurophysiological treatment for patients with refractory epilepsy, however, the mechanism of action remains unclear. Small animal positron emission tomography (PET) permits the monitoring of biochemical processes during multiple scans in the same animal. The aim of this pilot study was to explore the potential of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG)-PET to investigate the effect of acute and chronic VNS on glucose metabolism in the rat brain. One week after EEG and VNS electrode implantation, a baseline FDG-PET scan was acquired during which animals were not stimulated. Secondly, scans were taken after first activation of the VNS electrode (acute VNS) and after one week of continuous VNS (chronic VNS). On the same time points, images were obtained in a control group. After acquisition, PET images were manually fused with MRI data. Normalized brain activities and left/right activity ratios of different brain structures were compared between control measurements and VNS group. During acute VNS, glucose metabolism was significantly decreased in the left hippocampus (P<0.05). Significant increases were found in both olfactory bulbs (P<0.05). During chronic VNS, a significant decrease in left/right ratio in the striatum (P<0.05) was found. Acute and chronic VNS induced changes in glucose metabolism in regions important for seizure control (hippocampus and striatum). Our results promote further brain research on VNS using small animal PET in rats.

Animals↗
PubMed2005

Generator replacement in epilepsy patients treated with vagus nerve stimulation.

PURPOSE: In epilepsy patients treated with vagus nerve stimulation (VNS), the occurrence of end of battery life (EOBL), when the generator will no longer deliver any stimulation, was investigated with regard to seizure control. EOBL is preceeded by end of effective stimulation (EOES) when irregular stimulation may occur. METHODS: In 14/78 patients, treated with VNS at Ghent University Hospital, generators were replaced at different times following EOES or EOBL. We retrospectively analysed the time of occurrence of EOES and EOBL and seizure control before and after generator replacement. RESULTS: EOES or EOBL was indicated by loss of seizure control, decreased perception of stimulation and recurrence of depression in 3, 3 and 1/14 patient(s), respectively. In 2 and 1/14 patient(s), EOBL and premature generator failure, respectively, were detected during routine check-up at the epilepsy clinic. In 4/14 patients, generator replacement was performed before estimated EOES. Pre-replacement seizure control could not be regained in 2/14 patients in whom replacement had been postponed for several months. Estimation of EOES and EOBL occurrence proved difficult in individual patients. CONCLUSION: EOES or EOBL may be indicated by loss of seizure control, decreased or irregular perception of stimulation by the patient and loss of other VNS-induced effects. Postponing generator replacement may result into permanent loss of seizure control. In responders we suggest generator replacement before EOBL. Our results call for performance of prospective studies in larger patient groups that may eventually lead to general guidelines on the indication and timing of generator replacement.

Adult↗
PubMed2005

Chronic levetiracetam treatment early in life decreases epileptiform events in young GAERS, but does not prevent the expression of spike and wave discharges during adulthood.

PURPOSE: In Genetic Absence Epilepsy Rats from Strasbourg (GAERS), age-related absence seizures start to appear from postnatal day (PN) 30 concomitant with 'spike and wave discharges' (SWDs) appearing on cortical EEG recordings. The aim of this study was to investigate the effect of early chronic levetiracetam (LEV) treatment on the development of SWDs in young and adult GAERS. METHODS: From PN 23 until PN 60, LEV (54 mg/kg, i.p.) was administered once daily to GAERS (n=8), while control GAERS (n=7) received saline (0.9% NaCl, i.p.). All animals were implanted with four epidural EEG electrodes at PN 51. EEG was recorded for 3h daily, during the last 4 days of the treatment (PN 57-PN 60) and during 4 additional days after treatment had been terminated (PN 61-PN 64). The animals were monitored again at the age of 4 months (PN 120-PN 124), about 2 months after the last administration of LEV. RESULTS: During treatment, epileptiform events in the LEV group were significantly reduced (62%, P<0.05) in comparison with the control group. During the following 4 days, epileptiform events were reduced in the LEV group, with an average difference of 53% (P=0.064). Once the animals had reached adult age, there was no difference in epileptiform events between the LEV group and controls. CONCLUSION: In this study, chronic LEV administration induced a reduction in epileptiform events in young GAERS. This effect persisted to some extent after treatment cessation (PN 61-PN 64), which might indicate a slowing down of epileptogenic processes. However, at the age of 4 months all animals revealed a similar expression of epileptiform discharges.

Aging↗
PubMed2005

Steroids in intractable childhood epilepsy: clinical experience and review of the literature.

Steroids and adrenocorticotrophic hormone (ACTH) have been used for the treatment of infantile spasms for several years. However, the use of steroids in the treatment of epilepsy beyond infantile spasms has been limited to only a few studies. We report the experience with steroids in 32 children with intractable epilepsy, not including West syndrome. In 47% there was a decrease in seizure frequency, 25% became seizure free, 11% had a seizure reduction of >50% and 11% had a seizure reduction of <50%. Our study confirms the conclusions of few previous reports of effective adjunctive steroid treatment for children with intractable epilepsy. The possible side effects, however, especially during prolonged therapy remain an important concern.

Administration, Oral↗
PubMed2005

The acute and chronic effect of vagus nerve stimulation in genetic absence epilepsy rats from Strasbourg (GAERS).

PURPOSE: The aim of this study was to evaluate the efficacy of acute and chronic vagus nerve stimulation (VNS) in genetic absence epilepsy rats from Strasbourg (GAERS). This is a validated model for absence epilepsy, characterized by frequent spontaneous absences concomitant with spike and wave discharges (SWD) on the EEG. Although absences are a benign form of seizures, it is conceptually important to investigate the efficacy of VNS in a controlled study by using this chronic epilepsy model. METHODS: Both control and stimulated GAERS were implanted with five epidural EEG electrodes and a stimulation electrode around the left vagus nerve. In the first experiment, VNS was given when SWD occurred in the EEG; this was repeated the next day. A randomized crossover design (n = 8) was used. In the chronic experiment, GAERS underwent EEG monitoring during a first baseline week. During the second week, the treated group (n = 18) received VNS; controls (n = 13), on the other hand, only underwent EEG recordings. RESULTS: On day 1 of the acute VNS experiment, the mean duration of the SWD when VNS was applied was higher than in baseline conditions (p < 0.05). However, on day 2, there was no difference in mean duration of the SWD. In the chronic VNS experiment, no statistically significant differences were found between control and stimulated GAERS. CONCLUSIONS: Acute VNS applied shortly after the onset of SWD prolonged the mean duration of SWD in GAERS at least during the first day of VNS. Chronic stimulation hardly affected SWD in GAERS.

Animals↗
PubMed2005

Standards of care for adults with convulsive status epilepticus: Belgian consensus recommendations.

Status epilepticus (SE) is a significant health problem, affecting approximately 1,000 to 4,000 individuals per year in Belgium. A workshop was convened by a panel of neurologists from major Belgian centers to review the latest information relating to the definition, diagnosis and treatment of convulsive SE. The panelists sought to make recommendations for practising neurologists, but also primary care physicians and physicians in intensive care units when initiating emergency measures for patients with convulsive SE. As there is an association between prolonged seizures and a poor outcome, the importance of early (within the first 5 minutes of seizure onset) and aggressive treatment is to be stressed. In addition to general systemic support (airway, circulation), intravenous administration of the benzodiazepines lorazepam or diazepam is recommended as first-line therapy. Intramuscular midazolam may also be used. If SE persists, second-line drugs include phenytoin or valproate, and third-line drugs the barbiturate phenobarbital, the benzodiazepine midazolam, or the anaesthetics thiopental or propofol, or eventually ketamine. If the patient does not recover after therapy, monitoring of seizures should involve an electroencephalogram to avoid overlooking persistence of clinically silent SE. As a general rule, the intensity of the treatment should reflect the risk to the patient from SE, and drugs likely to depress respiration and blood pressure should initially be avoided. If initial treatment with a benzodiazepine fails to control seizures, the patient must be referred to the emergency unit and a neurologist should be contacted immediately.

Adult↗
PubMed2005

Cell therapy for neurological disorders: a comprehensive review.

Neurodegenerative diseases are characterized by the irreversible loss of neurons involved in networks, important for specific physiological functions. At present, several renewable cell sources stand in line to replace fetal brain cells as potential cell source for transplantation in the damaged brain. Recent developments raise the hope that selective populations of different neuronal phenotypes could be made "on demand". However, for every potential cell source there are still a lot of questions and drawbacks, which need to be resolved before a cell source could become the standard for clinical neuronal transplantation. The recent finding that the brain responds to damage by increased endogenous neurogenesis could prelude new "neurothrophic therapies", based on stimulating this endogenous repair. From preclinical studies it is evident that different disease mechanisms require different cell therapy approaches, depending on the underlying factor of the disease, the identity of neuronal systems that are involved and the complexity of networks that are affected. In this review the potential of different cell sources, including the endogenous progenitor cells, are discussed. Also results of preclinical and clinical transplantation studies in three different disease models are critically evaluated.

Animals↗