Dominic Heaney

Socioeconomic variation in incidence of epilepsy: prospective community based study in south east England

Abstract Objective: To determine the incidence of epilepsy in a general practice population and its variation with socioeconomic deprivation. Design: Prospective surveillance for new cases over an 18 or 24 month period. Participants: All patients on practice registers categorised for deprivation with the Carstairs score of their postcode. Setting: 20 general practices in London and south east England. Main outcome measure: Confirmed diagnosis of epilepsy. Results: 190 new cases of epilepsy were identified during 369 283 person years of observation (crude incidence 51.5 (95% confidence interval 44.4 to 59.3) per 100 000 per year). The incidence was 190 (138 to 262) per 100 000 in children aged 0-4 years, 30.8 (21.3 to 44.6) in those aged 45-64 years, and 58.7 (42.5 to 81.0) in those aged 65 years. There was no apparent difference in incidence between males and females. The incidence showed a strong association with socioeconomic deprivation, the age and sex adjusted incidence in the most deprived fifth of the study population being 2.33 (1.46 to 3.72) times that in the least deprived fifth (P=0.001 for trend across fifths). Adjustment for area (London v outside London) weakened the association with deprivation (rate ratio 1.62 (0.91 to 2.88), P=0.12 for trend). Conclusions: The incidence of epilepsy seems to increase with socioeconomic deprivation, though the association may be confounded by other factors. What is already known on this topic Epilepsy is associated with a wide range of markers of social and economic disadvantage A small number of epidemiological studies have confirmed this association but have not established the direction of causality What this study adds The incidence of epilepsy, adjusted for age and sex, in the most deprived fifth of the study population was 2.3 times that in the least deprived fifth Socioeconomic deprivation is an important risk factor for the development of epilepsy, though the results may partly reflect differences in incidence within and outside London

Antiepileptic drugs: generic versus branded treatments

Antiepileptic drugs (AEDs) are relatively cheap but high volumes of prescriptions mean that substantial drug-budget savings may be possible by switching from innovator brands to cheaper generic drugs. Such savings have been achieved in many other treatment areas. However, more caution may be needed in the case of epilepsy because of the narrow therapeutic range of most AEDs; clinical principles of prescribing, which include making only cautious and gradual changes to dosing; the health and socioeconomic impact of breakthrough seizures or toxicity; and the need for long-term consistency of supply. Many physicians and patient groups are insufficiently reassured by current definitions of similarity between generics and innovator brands. Switching to the cheapest generic AED may offer drug-budget savings that outweigh any risk to patient safety. But to date, this cost-benefit analysis has not been done. We propose that all changes to established principles of treating epilepsy are evidence based and that the risks of switching are clearly defined.

Cognitive consequences of childhood-onset temporal lobe epilepsy across the adult lifespan.

Objectives: To examine the influence of side of pathology and gender on changes in cognitive function across the adult lifespan in a homogenous sample of patients with mesial temporal lobe epilepsy (MTLE) associated with unilateral hippocampal sclerosis (HS). Methods: We retrospectively examined the neuropsychological profiles of 382 patients in 3 cohorts: cohort 1 aged 18–30 (n = 171), cohort 2 aged 31–45 (n = 170), and cohort 3 aged 46–65 (n = 41). All participants had medically intractable seizures associated with unilateral HS and an onset of epilepsy in childhood, with an average onset at 7 years. Results: There were no significant differences between the age cohorts on the measures of intellect, language, or memory. Duration of epilepsy (years) was not related to IQ, memory, or language scores in any group. Male subjects performed better than female subjects on verbal IQ, performance IQ, and naming tasks. Verbal learning and recall scores were worse in those with left than right HS. Conclusions: Our findings suggest that the profile of cognitive deficits associated with MTLE is already established as children with temporal lobe epilepsy enter adulthood. While memory and language skills are maximally affected, intellectual function is also compromised in MTLE. This profile appears to remain stable across the adult lifespan, at least until 60 years of age, despite the intractable nature of the seizures. Side of pathology and gender are significant mediating factors in shaping the profile of cognitive deficits associated with childhood-onset MTLE, with people with left-sided HS and female subjects particularly vulnerable to more widespread cognitive dysfunction.

Economic Evaluation of Epilepsy Treatment: A Review of the Literature

Summary: This article provides an overview of methods used and findings from economic analyses in epilepsy. Cost‐effectiveness studies have evaluated different drugs for monotherapy and add‐on therapy, and compared alternative treatment modalities for refractory epilepsy. The methodological characteristics of these studies are examined, and their results are compared and interpreted. Health outcome measures are defined and data sources described. Methods for assessing the direct and indirect costs, and/or cost savings, with a treatments use, are explored. Directions for future research are identified and discussed.

ILAE Commission on the Burden of Epilepsy, Subcommission on the Economic Burden of Epilepsy: Final Report 1998–2001

*School of Public Health, University of Texas-Houston, Houston, Texas, U.S.A.; †Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; ‡Epilepsy Research and Services, Chatswood, Australia; §Institute of Psychiatry, Kings College London, England; Department of Neurology, Comprehensive Epilepsy Program, University of Rochester Medical Center, Rochester, New York, U.S.A.; §§Swiss Epilepsy Centre, Zurich, Switzerland; **Department of Neurosurgery, University Hospital, Umea, Sweden; ††Department of Neurology, Jefferson Comprehensive Epilepsy Center, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A; and ‡‡Department of Clinical Neurological Sciences, University Hospital, London, Ontario, Canada

Long term monitoring in refractory epilepsy: the Gowers Unit experience

Introduction: Guidelines from the National Institute for Health and Clinical Excellence (NICE) and the International League Against Epilepsy recommend long term EEG monitoring (LTM) in patients for whom seizure or syndrome type is unclear, and in patients for whom it is proving difficult to differentiate between epilepsy and non-epileptic attack disorder (NEAD). The purpose of this study was to evaluate this recommended use of LTM in the setting of an epilepsy tertiary referral unit. Methods: This study reviewed the case notes of all admissions to the Sir William Gowers Unit at the National Society for Epilepsy in the years 2004 and 2005. A record was made of the type, duration and result of all LTM performed both prior to and during the admission. Pre- and post-admission diagnoses were compared, and patients were divided according to whether LTM had resulted in a change in diagnosis, refinement in diagnosis or no change in diagnosis. The distinction between change and a refinement in the diagnosis was made on the basis of whether or not this alteration resulted in a change in management. Results: 612 patients were admitted during 2004 and 2005, 230 of whom were referred for diagnostic clarification. Of these, LTM was primarily responsible for a change in diagnosis in 133 (58%) and a refinement of diagnosis in 29 (13%). In 65 (29%) patients the diagnosis remained the same after LTM. In those patients in whom there was a change in diagnosis, the most common change was in distinguishing epilepsy from NEAD in 73 (55%) and in distinguishing between focal and generalised epilepsy in 47 (35%). LTM was particularly helpful in differentiating frontal lobe seizures from generalised seizures and non-epileptic attacks. Inpatient ambulatory EEG proved as effective as video telemetry in helping to distinguish between NEAD, focal and generalised epilepsy. Discussion: The study revealed that LTM led to an alteration in the diagnosis of 71% of patients referred to a tertiary centre for diagnostic clarification of possible epilepsy. Although LTM is relatively expensive, time consuming and of limited availability, this needs to be balanced against the considerable financial and social cost of misdiagnosed and uncontrolled seizures. This service evaluation supports the use of performing LTM (either video or ambulatory) in a specialist setting in patients who present diagnostic difficulty.

An economic appraisal of carbamazepine, lamotrigine, phenytoin and valproate as initial treatment in adults with newly diagnosed epilepsy

Summary: We undertook an economic appraisal of four drugs used in monotherapy during the first 2 years of treatment for newly diagnosed patients with epilepsy: carbamazepine (CBZ), lamotrigine (LTG), phenytoin (PHT), and valproate (VPA). We adopted the cost‐minimization model because, although no single trial compares all four drugs directly, the clinical trials comparing two or more of these drugs in newly diagnosed cases show no significant difference in efficacy between the drugs in terms of seizure frequency: Considered in the cost analyses were frequency of side effects, retention rates, medical consultations, inpatient and accident and emergency costs, laboratory investigations, and drug changes. A Delphi panel provided the treatment pathways, including frequency of clinical consultations, second‐line monotherapy, and side‐effects management. A sensitivity analysis was performed, varying the assumptions on which the calculations were based. Analysis was completed for a prospective, intention‐to‐treat perspective and also for those patients continuing the initial drug. The direct medical costs of 2‐years therapy (intention‐to‐treat analysis) calculated for each trial were £795–829 for CBZ, £1,525‐2,076 for LTG, £736–768 for PHT, and £868–884 for VPA. A sensitivity analysis provided similar relative estimates. We found that LTG for newly diagnosed patients is significantly more expensive in direct health service costs incurred. This analysis incorporated seizure control, side effects, and tolerability. We recommend that a similar type of analysis be considered as part of all clinical trials of antiepileptic drugs in which efficacy of outcome is similar as a guide to assess optimal cost effectiveness.

Cost Minimization Analysis of Antiepileptic Drugs in Newly Diagnosed Epilepsy in 12 European Countries

Summary A recent United Kingdom cost minimization analysis (CMA) of four antiepileptic drugs (AEDs) used to treat newly diagnosed adult epilepsy demonstrated that a new drug, lamotrigine (LTG), incurred higher costs than carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA), whose costs were similar. This analysis took account of each drugs side‐effect and tolerability profile. The present analysis investigated the costs of treatment with LTG, CBZ, PHT, and VPA in 12 European countries. Data were derived from published sources and from a panel of locally based experts. When no published data were available, estimates were obtained using expert opinion by a consensus method. These data were incorporated into a treatment pathway model, which considered the treatment of patients during the first 12 months after diagnosis. The primary outcome considered was seizure freedom. Randomized controlled trials demonstrate that the drugs considered are equally effective in terms of their ability to achieve seizure freedom, and thus the most appropriate form of economic evaluation is a CMA. These trials provided data on the incidence of side effects, dosages, and retention rates. The economic perspective taken was that of society as a whole and the analysis was calculated on an “intent‐to‐treat” basis. Only direct medical costs were considered. In each country considered, LTG was twofold to threefold more expensive than the other drugs considered. A sensitivity analysis demonstrated that varying each of the assumptions (range defined by expert panels) did not significantly alter the results obtained.

Comparing the cost of epilepsy across eight European countries

To observe the degree to which prices for medical services and anti-epileptic drugs (AEDs) vary between eight European Union (EU) countries, to identify the factors that are likely to contribute to these variations and to consider the validity of international cost-of-illness comparisons. Cost-of-illness study methodology has been used to estimate the national cost of epilepsy in several developed countries. The validity of comparing these studies is unknown. Eight EU member countries were selected. Charges and prices were obtained for important aspects of medical care of patients with epilepsy including AEDs. The perspective taken was that of the major health care payer within each country. Prices were validated by a local panel of doctors expert in treating epilepsy. Prices for similar services were compared between countries. Charges and prices levied to health service payer vary widely between the eight countries considered. The cheapest and most expensive medical services vary by as much as 24 times, whereas the price of AED varies up to 4.4 times. These wide variations suggest that prices do not reflect the true cost of providing these important aspects of epilepsy treatment. International comparisons between national cost-of-illness estimates relying on such prices should be interpreted with caution.

Epilepsy at Work: Evaluating the Cost of Epilepsy in the Workplace

Most people with epilepsy indicate that their employment has been affected in some way by epilepsy. Surveys of the problems they encounter in daily life frequently reveal that people with epilepsy have difficulties getting jobs and endure a broad range of difficulties while at work (1,2). Over the past 30 years, many studies in the U.K. have investigated these difficulties by comparing the employment prospects of people with epilepsy with those of the general population. These studies highlighted a wide variety of problems that can be faced. Initial studies by Gordon and Russell (1958) (3) and Crombie et al. (1960) (4) revealed that people with epilepsy were less likely to be employed, and 540% of those of employable age reported serious difficulties with employment at some time. More recently, Scambler and Hopkins (1980) (5) showed excess unemployment rates for people with epilepsy, and Elwes et al. (6) demonstrated that in an area of England with a high unemployment rate, 48% of people with epilepsy who were potentially economically active were unemployed compared with 19% of ageand sex-matched individuals from the general population. Jacoby (1995) (7) noted that where seizures were well controlled and uncomplicated by other handicaps, people with epilepsy, in general, do not experience problems with employment. In a large community-based study of patients in a region of north England, she concluded that people with epilepsy are at a higher risk of unemployment and also of underemployment. In this study, 22% of men and 23% of women with epilepsy who were potentially economically active were unemployed. This compared with 12 and 8% in the general population, respectively (8). In this study it also was demonstrated that people with epilepsy are more likely to be employed in unskilled and manual occupations. From these studies and others, it is seen that the ability of people with epilepsy to work may be affected in sev-