Denis Verheulpen

Levetiracetam efficacy in epileptic syndromes with continuous spikes and waves during slow sleep : Experience in 12 cases

Summary:  Purpose: To assess the add‐on efficacy of levetiracetam on the EEG, behavior, and cognition of children with continuous spikes and waves during slow sleep (CSWS).

Coexistence of Idiopathic Rolandic Epilepsy and CSWS in Two Families

Summary:  Purpose: To report two families combining benign childhood epilepsy with centrotemporal spikes (BCECS) and cryptogenic epilepsy with continuous spike–waves during sleep (CSWS) in first‐degree relatives.

Cluster-based spike detection algorithm adapts to interpatient and intrapatient variation in spike morphology.

Visual quantification of interictal epileptiform activity is time consuming and requires a high level of experts vigilance. This is especially true for overnight recordings of patient suffering from epileptic encephalopathy with continuous spike and waves during slow-wave sleep (CSWS) as they can show tens of thousands of spikes. Automatic spike detection would be attractive for this condition, but available algorithms have methodological limitations related to variation in spike morphology both between patients and within a single recording. We propose a fully automated method of interictal spike detection that adapts to interpatient and intrapatient variation in spike morphology. The algorithm works in five steps. (1) Spikes are detected using parameters suitable for highly sensitive detection. (2) Detected spikes are separated into clusters. (3) The number of clusters is automatically adjusted. (4) Centroids are used as templates for more specific spike detections, therefore adapting to the types of spike morphology. (5) Detected spikes are summed. The algorithm was evaluated on EEG samples from 20 children suffering from epilepsy with CSWS. When compared to the manual scoring of 3 EEG experts (3 records), the algorithm demonstrated similar performance since sensitivity and selectivity were 0.3% higher and 0.4% lower, respectively. The algorithm showed little difference compared to the manual scoring of another expert for the spike-and-wave index evaluation in 17 additional records (the mean absolute difference was 3.8%). This algorithm is therefore efficient for the count of interictal spikes and determination of a spike-and-wave index.

Spike detection algorithm automatically adapted to individual patients applied to spike-and-wave percentage quantification.

OBJECTIVE To report an innovative spike detection algorithm that tailors its detection to the patient. Interictal epileptiform activity quantification was accomplished in the setting of epileptic syndromes with continuous spike and waves during slow sleep, which is a time-consuming task for the EEG analysis. METHODS The algorithm works in three steps. Firstly, a first spike detection is made with generic parameters. Secondly, the detected spikes are used to tailor the detection algorithm to the patient; and thirdly, the resulting patient-specific detection algorithm is used to analyze individual patient with high-quality detection. Therefore, the algorithm produces a patient-specific template -hence exhibiting improved performance metrics, without the need of a priori knowledge from the experts. RESULTS The system was first evaluated for EEG of three patients, against the scoring of three EEG experts, demonstrating similar performance. Later, it was evaluated against the spike and wave percentage evaluation of another expert for 17 additional records. The difference between the two evaluations was 4.4% on average, which is almost the same as the interexpert difference (4.7%). CONCLUSIONS We designed a fully automated and efficient spike detection algorithm, which is liable to trim down the specialists diagnostic time.

Acquired cognitive dysfunction with focal sleep spiking activity.

The syndrome of continuous spike‐waves during slow sleep (CSWS) is considered an epileptic encephalopathy in which the epileptiform abnormalities may contribute to progressive cognitive dysfunction. The characteristic electroencephalographic feature of the syndrome occurs during non‐REM sleep, and takes the form of continuous bilateral and diffuse slow spike‐waves that persist through all slow sleep stages. Using a case study design including clinical, neuropsychological, electroencephalographic, and positron emission tomography with 18F‐fluorodeoxyglucose (PET‐FDG) investigations, we describe the clinical and electroencephalographic findings in two patients who presented with nonsymptomatic epilepsy with unilateral spike‐waves during sleep. Both patients presented with a left unilateral motor neglect of the upper limb that was associated with unilateral CSWS activity over the right hemisphere, predominantly in the centrotemporal region. PET‐FDG studies during the active phase of CSWS showed right centrotemporal hypermetabolism in both cases. After treatment, a regression of the CSWS activity and an improvement of the cerebral FDG pattern were paralleled by a remission of the motor neglect. These cases demonstrate that the electroencephalographic pattern of CSWS in nonsymptomatic epilepsies is not necessarily diffuse and bilateral, and that focal unilateral CSWS activity can be associated with focal neuropsychological deficits. These findings add further evidence that the spectrum of clinical conditions associated with the electroencephalographic pattern of CSWS can include different forms of acquired cognitive disturbances that may be focal in nature.

A new spike-wave detection algorithm showing high sensitivity, low false positive rate and reduced computing time permits good detection of electrical status epilepticus during slow sleep (ESES) (abstract)

not submitted Sunday 28 August 2005 12:00 – 13:30 Salle 243 EILAT VIII Session Improving the Effectiveness of New AEDs: Pharmacokinetic Considerations New AEDs in the Elderly: Pharmacokinetic Optimization R.H. Levy 1) University Of Washington, USA. The use of new AEDs in the elderly presents numerous challenges. Pharmacokinetic (PK) optimization pertains to risk of PK and pharmacodynamic drug-drug interactions associated with the presence of co-morbid disorders and age-related altered pharmacokinetic behavior. The Metabolism and Transport Drug Interaction Database (http://dept.washington.edu/didbase) was used to perform a comparative analysis between new and old AEDs in term of risk for drug interactions. Concomitant-therapy considered in this analysis included antidepressants, cardiovascular agents (anticoagulants, antiplatelets), beta-blockers, diuretics, ACE inhibitors, angiotensin receptor antagonists, calcium channel blockers, statins and fibrates. Pronounced differences in drug interaction potential between new and old AEDs pertain to the consequences of enzyme induction by PHT, PB & CBZ on the disposition of SSRIs (paroxetine, sertraline, citalopram and mirtazapine), warfarin, calcium channel blockers, (verapamil, diltiazem, felodipine, nimodipine), some statins (atorvastatin, fluvastatin, lovastatin, simvastatin) and some beta blockers (bisoprodol, carvedilol, metoprolol, timolol). Plasma levels of these drugs would be expected to increase in patients switched from PHT, PB, CBZ to a newer AED. Co-medication with SSRIs, thiazide duretics and CBZ or OXC may be associated with hyponatremia which is of significance in the elderly. Dosage reductions in elderly patients may be required for gababentin, levetiracetam, oxcarbazepine, topiramate and zonisamide because of PK alterations in older patients. Pharmacokinetic Basis of Idiosyncratic Effects M. Bialer 1) Department Of Pharmaceutics, School Of Pharmacy, Faculty Of Medicine, The Hebrew University Of Jerusalem, Jerusalem, Israel. Idiosyncratic effects or idiosyncratic drug reaction (IDR) are a specific type of drug toxicity characterized by their delayed onset, low incidence and reactive metabolite formation. Idiosyncratic effects are unpredictable and can result in significant morbidity and sometimes mortality. These are often discovered after a drug approval during post marketing surveillance of phase IV clinical trials. Although they are dose-dependent in susceptible individuals, they do not occur at clinical doses with most patients. To date no animal or in vitro model exist to predict these adverse drug reactions. Therefore, the understanding of idiosyncratic effects mechanism is rather limited. Antiepileptic drugs (AEDs) have been recognized as being among the most common medications associated with severe cutaneous adverse reactions. Hypersensitivity reactions to the aromatic AEDs: phenytoin (PHT), carbamazepine (CBZ) appear to have immune etiology. One of the mechanisms for drug (AEDs) idiosyncratic hypersensitivity reaction centers around the concept of drug biotransformation to reactive metabolites that irreversibly modify cellular proteins. Thus, it has been proposed that aromatic AEDs may form metabolites that contain a reactive arene oxide moiety in their chemical structure, that could bind to cellular macromolecules and cause cell necrosis or secondary immunological response. Idiosyncratic reaction associated with lamotrigine (LTG) and felbamate (FBM), appears mechanistically distinct from PHT and CBZ hypersensitivity but may involve similar processes: active metabolites that form covalent adduct with vital proteins and macromolecules and subsequently starts a cascade of cell injury that may lead to tissue and organ injury and sometimes even death . One of theories behind FBM idiosyncratic effects is the formation of a reactive electrophilic metabolite atrophaldehyde or ATPAL (that contains a terminal double bond) that is capable of forming covalent protein adduct in vivo. The liver

A new simultaneously objective and patient-specific spike and wave detection algorithm based on template matching (abstract)

1,2,3 M. Raspall‐Chaure, 1,2,3 R. Chin, 1,2,3 B. Neville, and 1,2,3 R. Scott ( 1 Neurosciences Unit, Institute of Child Health, London, UK , 2 Epilepsy Unit, Great Ormond Street Hospital for Children NHS Trust, London, UK , 3 The National Centre for Young People with Epilepsy, Lingfield, UK )

Relationship between the characteristics of slow-wave components and cognitive impairment in rolandic epilepsy (abstract)

1 M. Sillanpää, 2 R. Kälviäinen, 3 T. Klaukka, 4 H. Helenius, and 5 S. Shinnar ( 1 Child Neurology And Public Health, University of Turku, Turku, Finland , 2 Neurology, Kuopio University Hospital, Kuopio, Finland , 3 Social Insurance Institution, Helsinki, Finland , 4 Biostatistics, University of Turku, Turku, Finland , 5 Neurology, Montefiore Medical Center, Bronx, USA )