Merel Wassenaar

Sudden cardiac arrest in people with epilepsy in the community: Circumstances and risk factors

Objective: To ascertain whether characteristics of ventricular tachycardia/fibrillation (VT/VF) differed between people with epilepsy and those without and which individuals with epilepsy were at highest risk. Methods: We ascertained 18 people with active epilepsy identified in a community-based registry of sudden cardiac arrest (SCA) with ECG-confirmed VT/VF (cases). We compared them with 470 individuals with VT/VF without epilepsy (VT/VF controls) and 54 individuals with epilepsy without VT/VF (epilepsy controls). Data on comorbidity, epilepsy severity, and medication use were collected and entered into (conditional) logistic regression models to identify determinants of VT/VF in epilepsy. Results: In most cases, there was an obvious (10/18) or presumed cardiovascular cause (5/18) in view of preexisting heart disease. In 2 of the 3 remaining events, near–sudden unexpected death in epilepsy (SUDEP) was established after successful resuscitation. Cases had a higher prevalence of congenital/inherited heart disease (17% vs 1%, p = 0.002), and experienced VT/VF at younger age (57 vs 64 years, p = 0.023) than VT/VF controls. VT/VF in cases occurred more frequently at/near home (89% vs 58%, p = 0.009), and was less frequently witnessed (72% vs 89%, p = 0.048) than in VT/VF controls. Cases more frequently had clinically relevant heart disease (50% vs 15%, p = 0.005) and intellectual disability (28% vs 1%, p < 0.001) than epilepsy controls. Conclusion: Cardiovascular disease rather than epilepsy characteristics is the main determinant of VT/VF in people with epilepsy in the community. SCA and SUDEP are partially overlapping disease entities.

Prognostic factors for medically intractable epilepsy: A systematic review

OBJECTIVE One third of all epilepsy patients have medically intractable epilepsy. Knowledge of prognostic factors that, in an early therapeutic stage of epilepsy, herald intractability could facilitate patient management. In this systematic review, we examined the evidence for independent prognostic factors of intractability in patients with epilepsy. METHODS MEDLINE and EMBASE were searched for cohort studies reporting on prognostic factors for medically intractable epilepsy. After selection of abstracts, full-text articles were obtained and their quality was assessed by two reviewers, using the QUIPS checklist. All independent prognostic factors in the individual studies were summarized. RESULTS Eleven cohort studies were included, of which ten hospital-based. Younger age at seizure onset, symptomatic etiology, high initial seizure frequency, medical history, epileptic EEG abnormalities, and failure of previous antiepileptic-drugs (AEDs) were documented as independent prognostic factors of intractability in at least 2 of the 11 studies; none of these factors was reported in all 11 studies. None of the studies considered genetic, neurobiological, or immunological factors. The studies were of moderate quality, mostly because they did not provide a conceptual model for the choice of predictors. Heterogeneity in study design, population, candidate prognostic factors, and outcome definitions precluded statistical pooling. CONCLUSIONS While potentially relevant prognosticators of medically intractable epilepsy have been identified, the evidence for these factors is not consistent. There is a need for well-designed prognostic population-based cohort studies that also include pharmacological, genetic, neurobiological, and immunological factors. A valid model for the early prediction of medically intractable epilepsy could improve patient management.

Comparative effectiveness of antiepileptic drugs in patients with mesial temporal lobe epilepsy with hippocampal sclerosis

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS) is a common epilepsy syndrome that is often poorly controlled by antiepileptic drug (AED) treatment. Comparative AED effectiveness studies in this condition are lacking. We report retention, efficacy, and tolerability in a cohort of patients with MTLE‐HS.

Photosensitivity in Dravet syndrome is under-recognized and related to prognosis

OBJECTIVE To detect determinants for photoparoxysmal EEG response (PPR) in SCN1A-related Dravet syndrome (DS). METHODS Data were studied from nationwide medical histories and EEGs of DS-patients (n=53; 31 males, age 2-19years). Detailed questionnaires on visual stimuli were completed by parents (n=49). RESULTS PPR was found in 22 patients (42%; median age 1.25yr), and repeatedly in 17%. PPR (17% of 249 intermittent photic stimulation (IPS)-EEGs) occurred more often with optimal IPS protocols (OR 2.11 [95%CI 1.09-4.13]) and in EEGs showing spontaneous epileptiform abnormalities (OR 5.08 [95%CI 2.05-12.55]). PPR-positive patients tended to be younger at first (p=0.072) and second seizure (p=0.049), showed severe intellectual disability (p=0.042), and had more often spontaneous occipital epileptiform abnormalities (p<0.001). Clinical sensitivity was reported in medical files in 22% of patients and by parents in 43% (self-induction 24%). Clinical or EEG proven visual sensitivity was detected in 65% of cases. CONCLUSIONS Sensitivity to visual stimuli is very common in DS and more often noticed by parents than confirmed by EEG. Detection of PPR improves with repetitive tests using accurate IPS protocols. SIGNIFICANCE Photosensitivity is an important feature in DS and seems to be a marker of the severity of the disorder. Therefore repeated standardized IPS should be encouraged.

Anti-epileptic drug changes and quality of life in the community.

Changes in anti‐epileptic drug (AED) regimens may indicate unsatisfactory treatment results such as insufficient seizure control or adverse effects. This inference underlies epilepsy management and research, yet current studies often do not account for AED changes. We assessed AED change patterns and their association with quality of life (QoL), as main outcome measure, in a community‐based setting.

Electro‐clinical criteria and surgical outcome: Is there a difference between mesial and lesional temporal lobe epilepsy?

Mesial temporal lobe epilepsy syndrome (MTLE) with specific electrophysiological and clinical characteristics and hippocampal sclerosis (HS) on MRI is considered the prototype of a syndrome with good surgical prognosis. Ictal onset zones in MTLE have been found to extend outside the hippocampus and neocortical seizures often involve mesial structures. It can, thus, be questioned whether MTLE with HS is different from lesional temporal epilepsies with respect to electro‐clinical characteristics and surgical prognosis. We assessed whether MTLE with HS is distinguishable from lesional TLE and which criteria determine surgical outcome.

Validity of health insurance data to identify people with epilepsy

BACKGROUND Large administrative databases may prove useful to assess epilepsy-related comorbidity and mortality. Despite their increased use, their validity as data source in epilepsy is yet under-ascertained. METHODS Achmea is a large Dutch health insurance company covering about 25% of the population. We performed a retrospective cohort study using data from the Achmea Health Insurance Database (AHID) over the period 2006-2009. To assess the validity of epilepsy codes in the AHID, we randomly invited 1000 individuals (age 18-75 years insured by Achmea), attending an epilepsy centre or a district hospital during 2006-2009, to participate. Informed consent was provided and 293 were eligible for inclusion. We compared the diagnostic codes for epilepsy in AHID with the diagnosis in their case-notes (reference standard). As additional measure of validity, we compared prevalence of epilepsy codes in AHID (based on anonymized data of all 26.297 subjects with this code in AHID) with epilepsy prevalence rates in the general Dutch population to estimate an age-specific standardized prevalence ratio. RESULTS We identified 293 participants with an epilepsy code in AHID. The majority (278) of them had a definite or possible diagnosis of epilepsy in the case-notes; i.e. a positive predictive value of 0.95 (95% CI 0.92-0.97). The overall prevalence of epilepsy codes in the AHID was slightly higher than the putative prevalence in the general Dutch population (7.4/1.000 vs. 6.8/1.000) with a Standardized Prevalence Ratio of 1.08 (95% CI: 1.08-1.09). CONCLUSIONS Our findings demonstrate the validity of AHID data for a diagnosis of epilepsy and confirm previous work on using administrative data for epilepsy research.