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Kristl Vonck

Publications and source records attributed to Kristl Vonck.

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

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↗
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

Lateralized anterior mesiotemporal lobe activation: semirandom functional MR imaging encoding paradigm in patients with temporal lobe epilepsy--initial experience.

PURPOSE: To prospectively demonstrate anterior mesiotemporal lobe (MTL) activation in healthy volunteers by using a semirandom memory-encoding paradigm and to prospectively compare lateralized functional magnetic resonance (MR) imaging activation with intracarotid amobarbital procedure (IAP) memory test results in patients with temporal lobe epilepsy (TLE) who were scheduled to undergo surgery. MATERIALS AND METHODS: The study was approved by a local ethics committee, and written informed consent was obtained from all subjects. Eight healthy volunteers and 18 patients with TLE who were scheduled for surgery were included in the functional MR imaging study involving the use of a memory-encoding paradigm with variable epoch lengths. Subjects were instructed to memorize new pictures that were mixed among pictures that they had seen before. Data analysis entailed computations of the contrast between the MTL activation induced by the new pictures and the MTL activation induced by the old pictures and of the lateralization index, defined as the relative difference in the number of activated voxels between the left and right MTLs. Lateralization indexes were compared between the patients and the volunteers and statistically correlated with the patients' IAP memory test results. To study deviations from perfect correspondence between the functional MR imaging- and IAP-derived lateralization indexes, orthogonal regression analysis was applied. Proportional relations for the patients with left-sided TLE and for those with right-sided TLE were calculated separately. RESULTS: The memory paradigm consistently activated the posterior and anterior MTL structures in both the healthy volunteers and the patients. Regression analysis revealed that functional MR imaging activation was stronger than the IAP results when it was lateralized to the contralateral MTL. This analysis also revealed a significant (P < .001) correlation between the functional MR imaging results and the IAP results in the patients with right-sided TLE but not in those with left-sided TLE (P > .1). CONCLUSION: The functional MR imaging memory-encoding paradigm consistently yielded MTL activation in the volunteers and the patients with TLE, but lateralized functional MR imaging activation was in concordance with the IAP results in only those patients with right-sided TLE.

Adult↗
PubMed2004

Enterocolitis: an adverse event in refractory epilepsy patients treated with levetiracetam?

INTRODUCTION: Levetiracetam (LEV) is a recently marketed novel anti-epileptic drug with a promising efficacy and safety profile. In this report we describe two patients who presented with enterocolitis and discuss the possible relationship with concurrent LEV intake. PATIENTS: In two patients. LEV was initiated to control refractory complex partial seizures (CPS). The first patient was treated with 1500 mg/day and complained of abdominal pain and weight loss 6 months later. Internal examination and colonoscopy revealed a punctate colitis. The second patient presented with bloody stool 1 month after LEV initiation. Colonoscopy showed punctate colitis. In both patients gastrointestinal symptoms disappeared following tapering of LEV. DISCUSSION: There are no reports in the literature describing colitis related to LEV intake. Three possible mechanisms of action are discussed. Colitis may be part of a hypersensitivity syndrome caused by LEV. Pharmacodynamic interactions with other anti-epileptic drugs, for example, carbamazepine may play a role. A haematological adverse event is another possibility since piracetam, a related molecule, has a known impact on erythrocytes and platelets. CONCLUSION: The close temporal relationship between initiation of LEV intake, symptomatic colitis and clinical improvement following LEV tapering, suggests that colitis may be a possible and previously undescribed adverse effect of LEV.

Adult↗
PubMed2004

Lessons for neuropsychology from functional MRI in patients with epilepsy.

This contribution aims to review the major findings of pre- and postsurgical functional magnetic resonance imaging (fMRI) in patients with refractory epilepsy from a neuropsychological perspective. We compared the contribution of fMRI with the intracarotid amytal procedure (IAP) with respect to functional mapping of language and memory in patients with therapy-resistant epilepsy. We conclude that using comprehensive language paradigms, fMRI has been able (1) to provide estimates of the degree of language lateralization including the degree of involvement of the nondominant hemisphere, (2) to provide information on the location of its activated network during expressive and receptive language, and (3) to help delineate eloquent language regions in the vicinity of the surgical target, thus preventing postoperative complications. The contribution of the frequently observed nondominant hemisphere activation to language should be explored and its clinical relevance determined. Evidence from fMRI studies is accumulating that reorganization of cognitive and motor function favors the activation of contralateral homotopic areas, although this process is far from understood. The exact functional contribution of atypical areas of activation should be investigated critically. In the presurgical evaluation process, detailed and reliable localization of language and memory functions of the individual patient is mandatory and should be the ultimate goal in the development of comprehensive clinical fMRI protocols.

Amobarbital↗
PubMed2003

Are psychotic symptoms related to vagus nerve stimulation in epilepsy patients?

Four patients with refractory epilepsy presented with psychotic symptoms following treatment with vagus nerve stimulation (VNS) to control seizures. Besides its anti-epileptic effect VNS has been shown to have an effect on various cognitive and behavioural functions. VNS is known to increase alertness and reduce sedation, which is independent from seizure control. VNS has also been shown to positively affect cognition and to exert strong antidepressant effects. Co-morbidity in epilepsy often comprises psychiatric illnesses. Increased psychiatric symptoms have mainly been described in association with successful outcome following epilepsy surgery as a result of 'forced normalisation'. Different hypotheses on the underlying aetiology of VNS-induced psychotic symptoms other than the previously described 'forced normalisation' are discussed.

Adult↗
PubMed2003

Neurostimulation for refractory epilepsy.

Neurostimulation is an emerging treatment for refractory epilepsy. To date the precise mechanism of action remains to be elucidated. Better insight in the mechanism of action may identify seizure types or syndromes that respond to such a treatment and may guide the search for optimal stimulation parameters and finally improve clinical efficacy. In the past ten years some progress has been made through neurophysiological, neuroanatomical, neurochemical and cerebral blood flow studies in patients and animals undergoing vagus nerve stimulation (VNS). Interesting results have been found in VNS-treated patients that underwent evoked potential measurements, cerebrospinal fluid investigation, neuropsychological testing and PET, SPECT and fMRI testing. Desynchronisation of abnormal synchronous epileptic activity is one of the hypotheses on the mode of action that might primarily be responsible for an anti-seizure effect. There is however increasing evidence from research and clinical observation that VNS might establish a true and long-term anti-epileptic effect. It has been shown that VNS influences neurotransmission in the brain and provokes long-term changes in cerebral blood flow in areas crucial for epileptogenesis such as the thalamus and medial temporal lobe structures. Deep brain stimulation (DBS) for epilepsy has regained interest. Central nervous system structures known to play a key role in the epileptogenic network such as the thalamus and subthalamic nucleus have been targeted. Another approach is to target the ictal onset zone such as the medial temporal lobe. At Ghent University Hospital 10 patients have been treated with long-term amygdalohippocampal DBS. Several hypotheses have been raised for the mechanism of action of DBS for refractory seizures. Seizure reduction may be due to a microlesion caused by electrode insertion or by provoking a reversible functional lesion due to the effect of electrical current on hyperexcitable tissue. Neurophysiological techniques such as evoked potentials monitoring and intraoperative single unit potential recordings may guide correct electrode placement, individual DBS titration and elucidation of the mechanims of action of DBS for epilepsy.

Animals↗
PubMed2002

Long-term amygdalohippocampal stimulation for refractory temporal lobe epilepsy.

Short-term deep brain stimulation (DBS) recently has been shown to be efficacious in refractory temporal lobe epilepsy. We (1) evaluated long-term DBS in medial temporal lobe structures in patients with normal magnetic resonance imaging (MRI) findings and (2) investigated the use of chronic DBS electrodes for the localization of the ictal onset zone before DBS. In three patients with complex partial seizures (CPSs), DBS electrodes were implanted in the amygdalohippocampal region to identify and subsequently stimulate the ictal onset zone. CPSs were compared before and after chronic DBS. Side effects were carefully monitored. DBS electrodes yielded high-quality electroencephalogram recordings showing unilateral seizure onset in medial temporal lobe structures. For all patients, unilateral amygdalohippocampal stimulation was performed. After a mean follow-up of 5 months (range, 3-6 months), all patients had a greater than 50% reduction in seizure frequency. In two patients, antiepileptic drugs could be tapered. None of the patients reported side effects. This open study demonstrates the feasibility of consecutive electroencephalographic recordings and DBS in medial temporal lobe structures using DBS electrodes. These results prompt further studies in a larger patient population to establish the efficacy and safety of chronic DBS as an alternative treatment for refractory temporal lobe epilepsy.

Adult↗