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1.
Colorectal Dis ; 22(12): 2252-2259, 2020 12.
Article in English | MEDLINE | ID: mdl-32683788

ABSTRACT

AIM: Pelviperineal wound complications frequently occur after salvage surgery for chronic pelvic sepsis despite using an omentoplasty. Sufficient perfusion of the omentoplasty following mobilization is essential for proper healing. This study investigated the impact on short-term clinical outcomes of fluorescence angiography (FA) using indocyanine green for assessment of omental perfusion in patients undergoing salvage surgery. METHOD: This was a comparative cohort study including consecutive patients who underwent combined abdominal and transanal minimally invasive salvage surgery with omentoplasty at a national referral centre for chronic pelvic sepsis between December 2014 and August 2019. The historical and interventional cohorts were defined based on the date of introduction of FA in April 2018. The primary outcome was pelviperineal non-healing, defined by the presence of any degree of pelviperineal infection at the final postoperative evaluation. RESULTS: Eighty-eight patients underwent salvage surgery with omentoplasty for chronic pelvic sepsis, of whom 52 did not have FA and 36 did have FA. The underlying primary disease was Crohn's disease (n = 50) or rectal cancer (n = 38), with even distribution among the cohorts (P = 0.811). FA led to a change in management in 28/36 (78%) patients. After a median of 89 days, pelviperineal non-healing was observed in 22/52 (42%) patients in the cohort without FA and in 8/36 (22%) patients in the cohort with FA (P = 0.051). Omental necrosis was found during reoperation in 3/52 and 0/36 patients, respectively (P = 0.266). CONCLUSION: After introduction of FA to assess perfusion of the omentoplasty, halving of the pelviperineal non-healing rate was observed in patients undergoing salvage surgery for chronic pelvic sepsis.


Subject(s)
Rectal Neoplasms , Sepsis , Cohort Studies , Fluorescein Angiography , Humans , Omentum/surgery , Sepsis/etiology , Sepsis/surgery
2.
Acta Neurol Scand ; 128(4): 273-80, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23461582

ABSTRACT

PURPOSE: Long-term antiepileptic drug use is associated with low bone mineral density (BMD), fractures and abnormalities in bone metabolism. We aimed at determining the prevalence of bone mineral disorders in patients with refractory epilepsy treated with antiepileptic drugs. METHODS: A cross-sectional survey was conducted in adult patients (n = 205) from a residential unit of a tertiary epilepsy centre. Screening for bone mineral disorders was performed with dual-energy X-ray absorptiometry (DXA) scan of spine and hip (including bone mineral density and vertebral fracture assessment) and laboratory measurements. Patient information regarding demography, epilepsy characteristics and medication use was recorded. Based on DXA T-scores, prevalence of bone mineral disorders (osteopenia and osteoporosis) was calculated. Correlations between DXA T-scores and epilepsy parameters were explored. RESULTS: Of the 205 patients, there were 10 dropouts. 80% (n = 156/195) of the patients had low BMD: 48.2% had osteopenia and 31.8% had osteoporosis. Of those having low BMD, 51.9% (n = 81/195) was between 18 and 50 years. The T-score of the femoral neck correlated significantly with total duration of epilepsy, cumulative drug load and history of fractures. Linear regression analysis showed that of the epilepsy-related parameters, only cumulative drug load significantly predicted low femoral neck T-score (P = 0.001). CONCLUSION: In this high-risk population, we obtained a very high prevalence of 80% of low BMD. Both men and women were affected as well as patients <50 years of age. This study illustrates the magnitude of the problem of bone mineral disorders in chronic epilepsy.


Subject(s)
Anticonvulsants/adverse effects , Bone Diseases, Metabolic/chemically induced , Bone Diseases, Metabolic/epidemiology , Inpatients , Osteoporosis/chemically induced , Osteoporosis/epidemiology , Absorptiometry, Photon , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Bone Density/drug effects , Chronic Disease/drug therapy , Cross-Sectional Studies , Epilepsy , Female , Humans , Male , Middle Aged , Prevalence , Regression Analysis , Young Adult
3.
Neurology ; 77(10): 938-44, 2011 Sep 06.
Article in English | MEDLINE | ID: mdl-21832213

ABSTRACT

OBJECTIVE: To study the relation between possibly altered whole brain topology and intellectual decline in chronic epilepsy, a combined study of neurocognitive assessment and graph theoretical network analysis of fMRI was performed. METHODS: Forty-one adult patients with cryptogenic localization-related epilepsy and 23 healthy controls underwent an intelligence test and fMRI with a silent-word generation paradigm. A set of undirected graphs was constructed by cross-correlating the signal time series of 893 cortical and subcortical regions. Possible changes in cerebral network efficiency were assessed by performing graph theoretical network analysis. RESULTS: Healthy subjects displayed efficient small world properties, characterized by high clustering and short path lengths. On the contrary, in patients with epilepsy a disruption of both local segregation and global integration was found. An association of more pronounced intellectual decline with more disturbed local segregation was observed in the patient group. The effect of antiepileptic drug use on cognitive decline was mediated by decreased clustering. CONCLUSIONS: These findings support the hypothesis that chronic localization-related epilepsy causes cognitive deficits by inducing global cerebral network changes instead of a localized disruption only. Whether this is the result of epilepsy per se or the use of antiepileptic drugs remains to be elucidated. For application in clinical practice, future studies should address the relevance of altered cerebral network topology in prediction of cognitive deficits and monitoring of therapeutic interventions.


Subject(s)
Cognition Disorders/physiopathology , Cognition Disorders/psychology , Epilepsies, Partial/physiopathology , Epilepsies, Partial/psychology , Intelligence Tests , Nerve Net/physiopathology , Adolescent , Adult , Anticonvulsants/adverse effects , Anticonvulsants/therapeutic use , Chronic Disease , Cognition Disorders/chemically induced , Epilepsies, Partial/drug therapy , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Nerve Net/drug effects , Young Adult
4.
Seizure ; 20(4): 285-91, 2011 May.
Article in English | MEDLINE | ID: mdl-21277231

ABSTRACT

INTRODUCTION: Epileptic seizures in stroke patients are a common complication and adversely affect neurological outcome. We tried to perform a trial aimed at preventing the development of late poststroke seizures using levetiracetam. Levetiracetam is assumed to have anti-epileptogenic properties and might be suitable to prevent late epileptic seizures in stroke patients. METHODS: Stroke patients with a cortical syndrome and a modified Rankin score ≥ 3 or NIHSS ≥ 6 were treated with either levetiracetam 1500 mg daily divided in two doses or placebo during 12 weeks following stroke. Treatment was started within 7 days following stroke onset. RESULTS: Only 16 patients were included in this trial. Problems during the execution of this prophylactic trial concerned the assessment of the occurrence of epileptic seizures, a very slow inclusion rate, the use of anticonvulsive co-medication, continuation of the trial medication after discharge, and the evaluation of possible side effects of the trial medication. DISCUSSION: Due to too few participants, no conclusions could be drawn regarding the ability of levetiracetam to prevent poststroke seizures. The problems encountered during execution of this trial seem to be inherent to performing a trial aimed at preventing the development of epileptic seizures in stroke patients. CONCLUSIONS: A prophylactic trial in stroke patients aimed at preventing poststroke seizures and epilepsy seems not feasible.


Subject(s)
Anticonvulsants/therapeutic use , Epilepsy/prevention & control , Piracetam/analogs & derivatives , Randomized Controlled Trials as Topic , Stroke/complications , Aged , Double-Blind Method , Epilepsy/etiology , Female , Humans , Levetiracetam , Male , Multicenter Studies as Topic/methods , Patient Selection , Piracetam/therapeutic use , Randomized Controlled Trials as Topic/methods
5.
J Mol Endocrinol ; 45(5): 341-53, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20819948

ABSTRACT

An increase in brain suppressor of cytokine signaling 3 (SOCS3) has been implicated in the development of both leptin and insulin resistance. Socs3 mRNA is localized throughout the brain, and it remains unclear which brain areas are involved in the effect of SOCS3 levels on energy balance. We investigated the role of SOCS3 expressed in the mediobasal hypothalamus (MBH) in the development of diet-induced obesity in adult rats. Socs3 mRNA was down-regulated by local injection of adeno-associated viral vectors expressing a short hairpin directed against Socs3, after which we determined the response to high-fat high-sucrose choice diet. In contrast to neuronal Socs3 knockout mice, rats with SOCS3 knockdown limited to the MBH showed increased body weight gain, larger amounts of white adipose tissue, and higher leptin concentrations at the end of the experiment. These effects were partly due to the decrease in locomotor activity, as 24 h food intake was comparable with controls. In addition, rats with Socs3 knockdown in the MBH showed alterations in their meal patterns: average meal size in the light period was increased and was accompanied by a compensatory decrease in meal frequency in the dark phase. In addition, neuropeptide Y (Npy) mRNA levels were significantly increased in the arcuate nucleus of Socs3 knockdown rats. Since leptin is known to stimulate Npy transcription in the absence of Socs3, these data suggest that knockdown of Socs3 mRNA limited to the MBH increases Npy mRNA levels, which subsequently decreases locomotor activity and alters feeding patterns.


Subject(s)
Energy Metabolism , Feeding Behavior , Hypothalamus/metabolism , Obesity/metabolism , Suppressor of Cytokine Signaling Proteins/genetics , Suppressor of Cytokine Signaling Proteins/physiology , Animals , Body Composition , Body Weight/physiology , Brain/metabolism , Down-Regulation , Gene Knockdown Techniques , HEK293 Cells , Humans , Insulin/metabolism , Leptin/metabolism , Male , Neuropeptide Y/genetics , Neuropeptide Y/metabolism , RNA, Messenger/genetics , RNA, Small Interfering , Rats , Rats, Wistar , Signal Transduction , Weight Gain
6.
Neurology ; 75(5): 395-402, 2010 Aug 03.
Article in English | MEDLINE | ID: mdl-20679633

ABSTRACT

BACKGROUND: An often underestimated cognitive morbidity in patients with epilepsy is language dysfunction. To investigate the neuronal mechanisms underlying neuropsychological language impairment, activation maps and functional connectivity networks were studied by fMRI of language. METHOD: Fifty-two patients with cryptogenic localization-related epilepsy and 27 healthy controls underwent neuropsychological assessment of IQ, word fluency, and text reading. fMRI was performed with a standard covert word-generation and text-reading paradigm. Functional connectivity analysis comprised cross-correlation of signal time series of the characteristic and most strongly activated regions involved in the language tasks. RESULTS: After careful selection, 34 patients and 20 healthy controls were found eligible for analysis. Patients displayed lower IQ, lower fluency word count, and lower number of words correctly read compared to controls. fMRI activation maps did not differ significantly between patients and controls. For the word-generation paradigm, patients with epilepsy had significantly lower functional connectivity than controls in the prefrontal network. Patients performing worse on the word-fluency test demonstrated a significantly lower mean functional connectivity than controls. Text reading demonstrated lower functional connectivity in patients with epilepsy in the frontotemporal network. Similarly, lower mean functional connectivity was observed in patients with lowest reading performance compared to controls. A relation between reduced functional connectivity and performance on word-fluency and text-reading tests was demonstrated in epilepsy patients. CONCLUSION: Impaired performance on language assessment in epilepsy patients is associated with loss of functional connectivity in the cognitive language networks.


Subject(s)
Brain/physiopathology , Epilepsies, Partial/physiopathology , Language Disorders/physiopathology , Adolescent , Adult , Brain Mapping , Case-Control Studies , Female , Humans , Intelligence , Intelligence Tests , Language , Language Tests , Magnetic Resonance Imaging , Male , Middle Aged , Neural Pathways/physiopathology , Neuropsychological Tests , Reading , Signal Processing, Computer-Assisted , Young Adult
7.
Eur J Neurol ; 16(11): 1173-7, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19538204

ABSTRACT

BACKGROUND AND PURPOSE: Complaints about side-effects of antiepileptic drugs (AEDs) may be overlooked in clinical practice. We assessed the value and risks of an active intervention policy for reported complaints in a randomized controlled pragmatic trial. METHODS: This randomized controlled pragmatic trial included 111 adults treated for epilepsy in seven general hospitals. They were considered well-managed by their treating physician, but reported moderate to severe complaints on a questionnaire (SIDAED, assessing SIDe effects in AED treatment). The intervention was adjustment of AED treatment (53 patients), either reduction of dose or switch of AED, versus continuation of treatment unchanged (58 control patients) during 7 months. Primary outcomes were quality of life (Qolie-10) and complaints score. Secondary outcome measures were the occurrence of seizures or adverse events. RESULTS: After 7 months, the relative risk (RR) for improvement in quality of life was 1.80 (1.04-3.12) for the intervention group compared to control and the RR of decrease in complaints was 1.34 (0.88-2.05). In 58% of patients randomized to adjustment, the medication had indeed been changed. DISCUSSION: In conclusion, despite a possible risk of seizure recurrence, adjustment of drug treatment in well-managed patients with epilepsy, who report considerable complaints, improves the quality of life.


Subject(s)
Anticonvulsants/administration & dosage , Anticonvulsants/adverse effects , Epilepsy/drug therapy , Quality of Life , Adult , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Male , Middle Aged , Patient Satisfaction , Seizures/drug therapy , Surveys and Questionnaires , Treatment Outcome
8.
Ned Tijdschr Tandheelkd ; 116(2): 97-101, 2009 Feb.
Article in Dutch | MEDLINE | ID: mdl-19280893

ABSTRACT

Nocturnal pins and needles and other sensory disturbances in the median nerve innervated fingers are caused by local pressure on this nerve in the carpal tunnel. Carpal tunnel syndrome is the most frequently encountered peripheral nerve entrapment. In The Netherlands, the prevalence of carpal tunnel syndrome is estimated 9% among adult women and 0.6% among adult men. Several risk factors have been identified. For dental professionals, the most relevant seem forceful use of the hand during scaling and extractions, use of vibrating ultrasonic equipment and frequent working with the wrist in flexion or in extension. The diagnosis of carpal tunnel syndrome is based on the characteristic complaints, confirmed preferably by abnormal electrophysiological tests. Depending on the degree of impact on daily functioning, treatment for carpal tunnel syndrome may be expectative, conservative or surgical. Adjustment of the working conditions may prevent the development of a carpal tunnel syndrome.


Subject(s)
Carpal Tunnel Syndrome/diagnosis , Carpal Tunnel Syndrome/therapy , Dentistry , Occupational Diseases/diagnosis , Occupational Diseases/therapy , Wrist/innervation , Carpal Tunnel Syndrome/prevention & control , Dentistry/methods , Diagnosis, Differential , Electrodiagnosis/methods , Humans , Netherlands , Neural Conduction/physiology , Occupational Diseases/prevention & control , Wrist/pathology
9.
Genes Brain Behav ; 8(1): 13-22, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18721260

ABSTRACT

The generation of motor activity levels is under tight neural control to execute essential behaviors, such as movement toward food or for social interaction. To identify novel neurobiological mechanisms underlying motor activity levels, we studied a panel of chromosome substitution (CS) strains derived from mice with high (C57BL/6J strain) or low motor activity levels (A/J strain) using automated home cage behavioral registration. In this study, we genetically mapped the expression of baseline motor activity levels (horizontal distance moved) to mouse chromosome 1. Further genetic mapping of this trait revealed an 8.3-Mb quantitative trait locus (QTL) interval. This locus is distinct from the QTL interval for open-field anxiety-related motor behavior on this chromosome. By data mining, an existing phenotypic and genotypic data set of 2445 genetically heterogeneous mice (http://gscan.well.ox.ac.uk/), we confirmed linkage to the peak marker at 79 970 253 bp and refined the QTL to a 312-kb interval containing a single gene (A830043J08Rik). Sequence analysis showed a nucleotide deletion in the 3' untranslated region of the Riken gene. Genome-wide microarray gene expression profiling in brains of discordant F(2) individuals from CS strain 1 showed a significant upregulation of Epha4 in low-active F(2) individuals. Inclusion of a genetic marker for Epha4 confirmed that this gene is located outside of the QTL interval. Both Epha4 and A830043J08Rik are expressed in brain motor circuits, and similar to Epha4 mutants, we found linkage between reduced motor neurons number and A/J chromosome 1. Our findings provide a novel QTL and a potential downstream target underlying motor circuitry development and the expression of physical activity levels.


Subject(s)
Chromosome Mapping , Motor Activity/genetics , Animals , Chromosomes/genetics , DNA Primers , Female , Genotype , Male , Mice , Mice, Inbred C57BL , Oligonucleotide Array Sequence Analysis , Polymorphism, Single Nucleotide , Receptor, EphA4/genetics
10.
Acta Neurol Scand ; 118(4): 232-9, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18460045

ABSTRACT

Objectives - The use of telencephalin as a possible marker for altered cortical function as demonstrated by functional MRI was investigated in a pilot study with 16 patients with localization-related epilepsy and secondarily generalized seizures. Materials and methods - Functional MRI of verbal working memory performance (Sternberg paradigm) and self-regulatory control processes (Stroop paradigm) was used to examine cortical activation in 16 patients with localization-related epilepsy and secondarily generalized seizures. Additionally, blood serum concentrations of soluble telencephalin (marker for neuronal damage) were determined. Results - In three patients (one temporal and two frontal focus), telencephalin was detected. All three patients had lower functional MRI activation in the frontotemporal region (P = 0.04), but not in other regions (P > 0.35) compared with patients without detectable telencephalin. Additionally, an association of levetiracetam and frontotemporal activation was observed. Conclusions - These preliminary data in a heterogeneous group suggest an association between decreased frontotemporal activation on fMRI and both detectable telencephalin serum levels and levetiracetam use. Future longitudinal studies with larger patient groups are required to confirm these observations. It is hypothesized that altered local function of the frontotemporal cortex in localization-related epilepsy might be better predicted by the biochemical marker telencephalin than epilepsy characteristics such as seizure focus.


Subject(s)
Brain/pathology , Cell Adhesion Molecules/blood , Epilepsies, Partial/blood , Epilepsies, Partial/pathology , Magnetic Resonance Imaging , Nerve Tissue Proteins/blood , Adult , Anticonvulsants/therapeutic use , Biomarkers/blood , Brain/drug effects , Epilepsies, Partial/drug therapy , Female , Humans , Levetiracetam , Male , Middle Aged , Neuropsychological Tests , Pilot Projects , Piracetam/analogs & derivatives , Piracetam/therapeutic use
11.
Ned Tijdschr Geneeskd ; 152(2): 76-81, 2008 Jan 12.
Article in Dutch | MEDLINE | ID: mdl-18265795

ABSTRACT

--Carpal tunnel syndrome (CTS) is the most frequently encountered peripheral nerve entrapment: about 10% of adult women and less than 1% of adult men in the Netherlands have a clinically and electrophysiologically confirmed CTS. --All medical and paramedical disciplines involved in the diagnosis and treatment of CTS in the Netherlands contributed to the development of a guideline for the diagnosis and treatment ofCTS. --Clinical diagnosis of CTS is based on a history of nocturnal pins and needles, numbeness and/or pain in the median nerve innervated area of the fingers and hand, which often causes the patient to awake. --Provocative tests do not contribute to the clinical diagnosis of CTS. --If invasive therapy is considered, such as corticosteroid injection or surgery, the clinical diagnosis must be confirmed by abnormal findings in electrophysiological tests. --Ultrasound or MRI of the wrist may be of diagnostic value when structural abnormalities in the carpal tunnel are suspected. Given the special expertise needed for ultrasound testing and the limited availability of MRI for CTS diagnostic purposes, these methods are not the first preference. --Depending on the degree of impact on daily functioning, treatment for CTS may be expectative, conservative (wrist splint or local steroid injections) or surgical (endoscopic or open techniques). --If CTS does not restrict daily functioning, adjustment of the working conditions will do. --Furthermore measures aimed at CTS prevention and treatment of an already existing work-related CTS are discussed.


Subject(s)
Carpal Tunnel Syndrome/diagnosis , Carpal Tunnel Syndrome/therapy , Practice Guidelines as Topic , Practice Patterns, Physicians' , Adrenal Cortex Hormones/therapeutic use , Carpal Tunnel Syndrome/prevention & control , Carpal Tunnel Syndrome/surgery , Diagnosis, Differential , Electrodiagnosis/methods , Humans , Netherlands , Neural Conduction/physiology , Wrist/innervation , Wrist/pathology
12.
Seizure ; 17(1): 19-26, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17618131

ABSTRACT

OBJECTIVE: Two of the most commonly prescribed new antiepileptic drugs as add-on therapy for patients with chronic refractory epilepsies are topiramate and levetiracetam. In regulatory trials, both drugs were characterized as very promising new antiepileptic drugs. However, results from these highly controlled short-term clinical trials cannot simply be extrapolated to everyday clinical practice, also because head-to-head comparisons are lacking. Therefore, results from long-term open label observational studies that compare two or more new AEDs are crucial to determine the long-term performance of competing new antiepileptic drugs in clinical practice. METHOD: We analyzed all patients referred to a tertiary epilepsy centre who had been treated with topiramate from the introduction of the drug in spring 1993 up to a final assessment point mid-2002 and all patients who had been treated with LEV in the same centre from the introduction of the drug in early 2001 up to a final assessment point end-2003 using a medical information system. RESULTS: Three hundred and one patients were included for levetiracetam and 429 patients for TPM. Retention rate after 1 year was 65.6% for LEV-treated patients and 51.7% for TPM-treated patients (p=0.0015). Similarly, retention rates for LEV were higher at the 24-month mark: 45.8% of LEV-treated patients and 38.3% of TPM-treated patients were still continuing treatment (p=0.0046). Adverse events led to drug discontinuation in 21.9% of TPM-treated patients compared to 6.0% of LEV-treated patients (p<0.001). The number of patients discontinuing treatment because of lack of efficacy was similar for both groups. Seizure freedom rates varied between 11.6 and 20.0% for TPM and between 11.1 and 14.3% for LEV per 6-months interval. Several important AED specific adverse events leading to drug discontinuation were identified, including neurocognitive side effects from TPM and mood disorders from LEV. CONCLUSION: The retention rate for LEV is significantly higher than for TPM. LEV had a more favourable side effect profile than TPM with comparable efficacy. Patients on TPM discontinued treatment mainly because of neurocognitive side effects. In the treatment with LEV, the effects on mood must not be underestimated.


Subject(s)
Anticonvulsants/therapeutic use , Epilepsy/drug therapy , Fructose/analogs & derivatives , Piracetam/analogs & derivatives , Adolescent , Adult , Age of Onset , Aged , Anticonvulsants/adverse effects , Child , Child, Preschool , Cognition/drug effects , Cognition/physiology , Epilepsy/psychology , Female , Fructose/adverse effects , Fructose/therapeutic use , Humans , Infant , Levetiracetam , Long-Term Care , Magnetic Resonance Imaging , Male , Middle Aged , Piracetam/adverse effects , Piracetam/therapeutic use , Tomography, X-Ray Computed , Topiramate
13.
Acta Neurol Belg ; 107(1): 22-5, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17569230

ABSTRACT

The ictal bradycardia syndrome is an uncommon diagnosis in which bradycardia is accompanied by simultaneous epileptic discharges in the EEG. We describe a patient who was referred to the emergency ward because of syncope. Ictal semeiology and EEG-EG findings are discussed and compared with those published in the literature. Therapeutic options are discussed in relation with those published in the literature. The ictal bradycardia syndrome is probably underdiagnosed, while its recognition is of utmost importance because of potential life threatening complications such as asystole. Up to now, its aetiology is poorly understood, its ictal semeiology is often described insufficiently and its therapy is still discussed.


Subject(s)
Bradycardia/etiology , Bradycardia/physiopathology , Cerebral Cortex/physiopathology , Epilepsy/complications , Epilepsy/physiopathology , Evoked Potentials/physiology , Autonomic Nervous System Diseases/etiology , Autonomic Nervous System Diseases/physiopathology , Autonomic Pathways/physiopathology , Electroencephalography , Epilepsy/diagnosis , Humans , Male , Middle Aged , Syndrome , Temporal Lobe/physiopathology
15.
Epilepsy Behav ; 10(2): 296-303, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17317325

ABSTRACT

OBJECTIVE: For the treatment of patients with chronic refractory epilepsies, development of new antiepileptic drugs is crucial. Three regulatory trials have demonstrated that add-on levetiracetam is efficacious in patients with localization-related epilepsy. However, results from these highly controlled short-term clinical trials cannot simply be extrapolated to everyday clinical practice. Therefore, more information is needed about the long-term profile of a new antiepileptic drug in clinical practice. METHOD: We analyzed all patients who had been treated with levetiracetam in the Epilepsy Centre Kempenhaeghe from the introduction of the drug in early 2001 up to a final assessment point, at the end of 2003, using a medical information system. RESULTS: In total, 301 patients were included. One hundred thirty-eight patients (45.8%) discontinued LEV treatment during the 24-month follow-up period. Reasons for discontinuation were lack of efficacy in 15.9% of patients, adverse events in 6.0% of patients, and a combination of lack of efficacy and adverse events in 16.3% of patients. By Kaplan-Meier survival analysis, the continuation rate was 65.6% after 1 year and 45.8% after 2 years. About 15% of patients in this highly refractory group had a 3-month remission, whereas 10% of patients became seizure-free for longer periods. The most frequently reported side effects at the time of discontinuation were mood disorders, tiredness, and sleepiness. Variables predicting (dis)continuation of levetiracetam treatment could not be identified. CONCLUSION: Levetiracetam is a new antiepileptic drug that appears to be a useful add-on treatment in patients with refractory epilepsy. Its side effect profile is mild, with mood disorders being the most dominant adverse event.


Subject(s)
Anticonvulsants/therapeutic use , Epilepsy/drug therapy , Piracetam/analogs & derivatives , Adolescent , Adult , Aged , Anticonvulsants/administration & dosage , Anticonvulsants/adverse effects , Child , Child, Preschool , Drug Resistance , Drug Therapy, Combination , Epilepsy/complications , Female , Follow-Up Studies , Humans , Infant , Levetiracetam , Male , Mental Disorders/complications , Middle Aged , Piracetam/administration & dosage , Piracetam/adverse effects , Piracetam/therapeutic use , Referral and Consultation , Seizures/epidemiology , Seizures/prevention & control , Survival Analysis
16.
Seizure ; 16(2): 153-9, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17178458

ABSTRACT

OBJECTIVE: To evaluate risk factors for sudden and unexpected death in epilepsy (SUDEP) in a high-risk population, i.e. patients treated in a Dutch tertiary referral center for epilepsy. METHODS: All patients who died between January 1999 and April 2004 while under treatment of the epilepsy center were identified. Based on clinical data, deaths were classified as definite, probable, possible or non-SUDEP. Potential risk factors were compared in SUDEP cases and non-SUDEP cases. RESULTS: SUDEP incidence was 1.24 per 1000 patient years. SUDEP patients died at a younger age than patients from the control group of non-SUDEP deaths with epilepsy and had an earlier onset of epilepsy. However, the frequently mentioned factors in previous studies, i.e. male sex, generalized tonic-clonic seizures, high seizure frequency, specific AEDs, polytherapy with several AEDs, mental retardation, psychiatric illness and psychotropic comedication, were not found to be correlated with SUDEP. CONCLUSIONS: Even in this high-risk population of patients with refractory epilepsy, treated in a tertiary referral center, SUDEP is not a frequently occurring phenomenon. Specific risk factors could not be identified within an already high-risk population.


Subject(s)
Death, Sudden/epidemiology , Epilepsy/mortality , Adolescent , Adult , Age Factors , Aged , Anticonvulsants/therapeutic use , Child , Child, Preschool , Epilepsy/classification , Epilepsy/drug therapy , Humans , Middle Aged , Netherlands , Retrospective Studies , Risk Factors
17.
Seizure ; 16(1): 1-7, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17134918

ABSTRACT

INTRODUCTION: Several risk factors for sudden unexplained death in epilepsy patients (SUDEP) have been proposed, but subsequent work has yielded conflicting data. The relative importance of various risk factors for SUDEP was never explored. The aim of this study is to review systematically risk factors for SUDEP and also to determine their relevance for SUDEP by calculating relative risk factor ratios. METHODS AND MATERIALS: Authors performed a literature-search on "SUDEP" in Medline, the Cochrane Library and EMBASE. Studies with unknown number of SUDEP cases or with less than five SUDEP cases and reviews were excluded from further analysis. The value of each paper was assessed, based on the quality of the study and the reliability of the diagnosis of SUDEP. This value ranged from 1 (low quality) to 10 (high quality). Papers with a value below 7 were eliminated for further analysis. For each analysed factor, a risk factor ratio was determined, with a higher ratio for a stronger risk factor. RESULTS: A number of strong risk factors for SUDEP: young age, early onset of seizures, the presence of generalized tonic clonic seizures, male sex and being in bed. Weak risk factors for SUDEP: prone position, one or more subtherapeutic bloodlevels, being in the bedroom, a strucural brain lesion and sleeping. CONCLUSIONS: In this study, authors have designed a quality scale to select papers. The relative importance of risk factors for SUDEP is demonstrated.


Subject(s)
Death, Sudden/etiology , Epilepsy, Tonic-Clonic/epidemiology , Epilepsy/complications , Age Factors , Age of Onset , Female , Humans , Male , Risk Factors , Sex Factors , Sleep
18.
Br J Pharmacol ; 149(7): 815-27, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17043670

ABSTRACT

Mutations in the human melanocortin (MC)4 receptor have been associated with obesity, which underscores the relevance of this receptor as a drug target to treat obesity. Infusion of MC4R agonists decreases food intake, whereas inhibition of MC receptor activity by infusion of an MC receptor antagonist or with the inverse agonist AgRP results in increased food intake. This review addresses the role of the MC system in different aspects of feeding behaviour. MC4R activity affects meal size and meal choice, but not meal frequency, and the type of diet affects the efficacy of MC4R agonists to reduce food intake. The central sites involved in the different aspects of feeding behaviour that are affected by MC4R signalling are being unravelled. The paraventricular nucleus plays an important role in food intake per se, whereas MC signalling in the lateral hypothalamus is associated with the response to a high fat diet. MC4R signalling in the brainstem has been shown to affect meal size. Further genetic, behavioural and brain-region specific studies need to clarify how the MC4R agonists affect feeding behaviour in order to determine which obese individuals would benefit most from treatment with these drugs. Application of MCR agonists in humans has already revealed side effects, such as penile erections, which may complicate introduction of these drugs in the treatment of obesity.


Subject(s)
Appetite Regulation , Melanocortins/metabolism , Obesity/metabolism , Receptor, Melanocortin, Type 4/genetics , Receptor, Melanocortin, Type 4/metabolism , Signal Transduction , Agouti-Related Protein , Animals , Anti-Obesity Agents/pharmacology , Appetite Depressants/pharmacology , Appetite Regulation/drug effects , Brain/metabolism , Diet , Energy Intake , Feeding Behavior , Food Preferences , Humans , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Ligands , Mice , Mice, Transgenic , Mutation , Nutritional Physiological Phenomena , Obesity/genetics , Obesity/physiopathology , Pro-Opiomelanocortin/genetics , Pro-Opiomelanocortin/metabolism , Receptor, Melanocortin, Type 3/genetics , Receptor, Melanocortin, Type 3/metabolism , Receptor, Melanocortin, Type 4/drug effects , Signal Transduction/drug effects , Time Factors
19.
Seizure ; 15(4): 242-8, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16551504

ABSTRACT

OBJECTIVES: Side-effects of anti-epileptic drugs (AEDs) may be overlooked in patients with epilepsy in everyday clinical practice. The aim of this study was to assess the prevalence and severity of subjective complaints in patients who were considered to be well-controlled and to assess whether these complaints are related to medication, personality traits, or other determinants. METHODS: We included patients with epilepsy who were considered to be well-controlled in a cross-sectional study in seven hospitals in the Netherlands. Their medication had not been changed for six months and an apparent reason to change the medication was lacking at the time of enrolment. Subjective complaints were assessed with a 46-item questionnaire. Using multivariable linear regression modeling, we assessed whether patient characteristics, epilepsy characteristics, medication, quality of life (Qolie-10), and personality traits (SCL-90) explained the presence and severity of complaints. RESULTS: Of 173 included patients, 67% reported moderate to severe subjective complaints on the questionnaire. Cognitive complaints were reported most frequently. Multivariate modeling showed that 61% of the variance in reported complaints could be explained by included determinants. The prevalence and severity of complaints was associated with AED polytherapy and higher scores on psycho neuroticism. CONCLUSIONS: Patients who were considered to be well-controlled proved to report an unexpectedly high number of subjective complaints. Both medication and aspects of personality contributed to the level of complaints. Our study illustrates that subjective side-effects are easily overlooked in everyday clinical practice, possibly because in practice a generally phrased question is used to detect side-effects.


Subject(s)
Anticonvulsants/adverse effects , Cognition Disorders/epidemiology , Epilepsy/drug therapy , Patient Satisfaction , Quality of Life , Adolescent , Adult , Cognition/drug effects , Cognition Disorders/etiology , Cross-Sectional Studies , Drug Therapy, Combination , Epilepsy/psychology , Female , Humans , Linear Models , Male , Middle Aged , Multivariate Analysis , Surveys and Questionnaires
20.
Ned Tijdschr Geneeskd ; 148(26): 1269-72, 2004 Jun 26.
Article in Dutch | MEDLINE | ID: mdl-15279206

ABSTRACT

Two male patients, 46 and 62 years of age, were brought to the emergency department on a hot summer's day. Both wore excessive clothing. The first patient had a temperature of 43 degrees C and was comatose. Heteroanamnesis indicated that he was suffering from schizophrenia. Although the prognosis seemed to be poor, his condition improved after treatment in intensive care, consisting of cooling and supportive treatment, but the patient had considerable permanent neurological impairment. The second patient had a temperature of 40.3 degrees C, was confused and had an atactic gait. He was cooled immediately and recovered swiftly without complications. Heat stroke is a life-threatening illness, which is defined as a body temperature above 40 degrees C and central nervous-system dysfunction. Heat stroke may be attended by many serious complications, including multi-organ failure and residual brain damage. Prompt recognition and rapid treatment, consisting of adequate cooling, are required.


Subject(s)
Body Temperature , Brain Damage, Chronic/etiology , Heat Stroke/complications , Heat Stroke/diagnosis , Heat Stroke/therapy , Humans , Male , Middle Aged , Multiple Organ Failure/etiology , Time Factors , Treatment Outcome
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