SEARCH

SEARCH BY CITATION

Keywords:

  • Temporal trends;
  • Mortality;
  • Epilepsy;
  • Epidemiology;
  • Population studies

Summary

  1. Top of page
  2. Summary
  3. Aims
  4. Methodology
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

Purpose:  It is now generally accepted that people with epilepsy are at increased risk of premature death compared with peers in the general population. It has, however, not been clearly established how this risk changes over time, nor whether mortality rates have been changing over time.

Methods:  We carried out a systematic review: (1) To determine the pattern of change of mortality risk relative to the general population in people with epilepsy in the course of their condition as measured by standardized mortality ratios (SMRs), by reviewing longitudinal prospective cohort studies. (2) To establish whether there have been any changes in reported mortality rates for epilepsy in general populations over time. This was complemented by comparison of SMRs in people with epilepsy in the same types of source populations (population-based, hospital-based, and institutional studies) in different time periods to ascertain any changes in reported mortality rates.

Results:  The SMR is highest in the initial years after diagnosis and subsequently decreases. There is a suggestion that there may be an increase after 10 years from diagnosis despite the fact that the majority of people in these cohorts are in long-term remission. There is no evidence that either the overall SMR or the mortality rate of people with epilepsy has changed significantly over time.

Discussion:  Further population and cohort studies are needed to confirm these findings.

Although it is generally accepted that people with epilepsy are at increased risk of premature death compared with the general population (Cockerell et al., 1994; Hauser et al., 1980; Tomson, 2000; Gaitatzis et al., 2004), it has not been clearly established how this risk changes over the course of the condition. It is assumed that most early deaths in epilepsy are due to the underlying cause of the epilepsy, whereas any later increase in mortality rate is due primarily to the epilepsy itself (Hauser et al., 1980; Forsgren et al., 2005), despite the fact that the majority of people become seizure free. If this is the case, one would expect to see evidence of decreasing mortality rates in the population with epilepsy over the last 50 years and in particular in the last 20 years when more treatment options for epilepsy have become available.

The standardized mortality ratio (SMR), which is defined as the ratio of the observed deaths in the study population to the expected deaths if the group had experienced the same age- and sex-specific deaths as the population from which it came, is commonly used as a measure of mortality.

Much of the variation in reported SMRs in people with epilepsy is dependent on the source population. In general, institutional studies report the highest SMRs, with the lowest coming from general population based studies. In 21 identified studies, institutional studies showed wider variation in mortality rates (SMR 1.9–5.1) than population-based studies (SMR 1.3–3.1) (Shackleton et al., 2002).

The direct comparison of SMRs in different studies is problematic, as the SMR is calculated by indirect standardization using the age and gender distribution of the group with epilepsy, which may differ between studies. It has been argued that these potential differences may invalidate direct comparison of SMRs derived from distinct populations (Logroscino & Hesdorffer, 2005). Even taking this into account, some insight may be derived by comparing SMRs between studies of similar populations as a crude measure of changes of mortality between different time periods, particularly as this is the only method of comparison available.

Aims

  1. Top of page
  2. Summary
  3. Aims
  4. Methodology
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References
  • 1
    To determine the pattern of change of mortality risk relative to the general population in people with epilepsy in the course of their condition as measured by SMRs, by means of longitudinal prospective cohort studies.
  • 2
    To establish whether there have been any changes in reported mortality rates for people with epilepsy over time.

We have subdivided our analyses according to source populations (population-based, hospital-based, and institutional studies).

Methodology

  1. Top of page
  2. Summary
  3. Aims
  4. Methodology
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

Research strategy

A search of PubMed and MEDLINE for suitable articles was carried out. Initially the terms “epilepsy,”“mortality,”“premature death,”“death,” and “fatality,” excluding animal studies, were searched and papers written in English and French were reviewed. This identified 2,505 articles, and this number was reduced by excluding papers whose primary focus was status epilepticus or sudden unexpected death in epilepsy (SUDEP). Titles and abstracts of all relevant articles were reviewed and the bibliographies of key papers were perused to identify other relevant studies. A further search of the literature was performed using the search terms “epilepsy,”“mortality,” and “trends.” The reprint collections of the authors were also reviewed for further potential references.

Results

  1. Top of page
  2. Summary
  3. Aims
  4. Methodology
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

Changes in SMR in people with epilepsy over the course of the condition

Population-based studies

Eight population-based studies of mortality among people with epilepsy have been reported (Table 1). Three of these studies (Zielinski, 1974; Loiseau et al., 1999; Ding et al., 2006) have only short follow-up periods, so no conclusions about changes in mortality rates with duration of epilepsy can be drawn from these. The oldest study, a prevalent cohort from Poland (Zielinski, 1974), had a follow-up of 3 years; the Gironde study looked at the SMR in people with epilepsy 1 year after diagnosis (Loiseau et al., 1999), and in the other, a prospective study of a predominantly prevalent cohort in rural China, the median follow-up was 25 months (Ding et al., 2006).

Table 1.   Population studies of mortality in people with epilepsy with standardized mortality ratios (with 95% confidence intervals)
ReferenceCountrySMRLength of follow-upAgesComments
  1. aTwo papers reported mortality rates for the NGPSE cohort, after a median follow-up of 6.9 and 11.8 years, respectively.

  2. bDefinite epilepsy.

  3. cDefinite and possible epilepsy.

Zielinski (1974)Poland1.83 yearsAllRetrospective prevalent cohort
Hauser et al. (1980)United States2.3 (1.9–2.6)Mean 13 years (0–29 years)AllHistoric incident cohort (Rochester)
Cockerell et al. (1994)aUnited Kingdom3.0 (2.5–3.7)b 2.5 (2.1–2.9)cMedian 6.9 yearsAllProspective incident cohort (NGPSE) 1984–1992
Olafsson et al. (1998)Iceland1.6 (1.2–2.2)Mean 28 yearsAllHistoric incident cohort
Loiseau et al. (1999)France4.1 (2.5–6.2)1 yearAllProspective, incident cohort 1 year mortality
Lindsten et al. (2000)Sweden2.5 (1.2–3.2)Mean 7.9 years≥17 yearsProspective incident cohort with first seizure
Lhatoo et al. (2001)aUnited Kingdom2.6 (2.1–3.0)b 2.1 (1.8–2.4)cMedian 11.8 yearsAllNGPSE cohort 1984–1997
Camfield et al. (2002)Canada5.3 (2.3–8.3)Median 13.9 years for survivors<17 yearsHistoric incident cohort
Ding et al. (2006)China3.9 (3.8–3.9)Median 25 months>2 yearsProspective incident and prevalent cohort

A Swedish study identified 107 patients, newly diagnosed with unprovoked epileptic seizures between 1985 and 1987, and followed them until death or until 1996 (Lindsten et al., 2000). The overall SMR was significantly increased [2.5; 95% confidence interval (CI) 1.2–3.2]. In the first year the SMR was 7.3 (95% CI 4.4–12.1) and in the second year it was 3.6 (95% CI 1.6–8.1), following which the SMR decreased to a plateau level of between 1 and 2 for years 4–9 of follow-up (apart from year 4 at which the SMR rose slightly above 2 and year 6 at which it dropped below 1). In years 9–11, however, the SMR was 5.4 (95% CI 2.7–11.2).

In The National General Practice Study of Epilepsy and Epileptic Seizures (NGPSE), an incident cohort of 792 patients with definite or possible epilepsy, identified between 1984 and 1987, was followed for 14 years. The initial mortality data were reported at a median follow-up of 6.9 years, when the SMR for patients with definite epilepsy was 3.0 (95% CI 2.5–3.7) and for those with definite or possible epilepsy was 2.5 (95% CI 2.1–2.9). The SMR for those with definite or possible epilepsy combined was maximum at 1 year since diagnosis at 5.1 (95% CI 3.8–6.5), decreasing to 2.5 (95% CI 1.5–3.9) at 4 years and 1.3 (95% CI 0.7–2.0) at >5 years (Cockerell et al., 1994).

At a median follow-up of 11.8 years the overall SMR (definite and possible epilepsy) was 2.1 (95% CI 1.8–2.4). The SMR decreased to 1.3 (95% CI 0.9–1.7) at years 4–9 and was slightly higher at 1.6 (95% CI 1.1–2.2) at years 9–14 years after diagnosis. This suggestion of a trend was more marked for those with definite epilepsy (n = 564), for whom the SMR was significantly elevated at all points of follow-up (Lhatoo et al., 2001). It has also been shown in this cohort that people with epilepsy have a decreased life expectancy dependent on the severity of the epilepsy (Gaitatzis et al., 2004).

A Canadian study followed 692 children (up to 16 years of age) who developed epilepsy between 1977 and 1985, for a median of 13.9 years (range 0–22.5 years) from the time of diagnosis (Camfield et al., 2002). The SMR from 1980–1989 (corresponding to 0–12 years since diagnosis) was 5.3 (95% CI 2.3–8.3) and for 1990–1999 (5–22 years since diagnosis) was 8.8 (95% CI 4.2–13.4). Twenty years after the onset of seizures 6.1% (95% CI 3.0–9.2) of the cohort had died.

In a retrospective Icelandic population-based study of 224 children and adults, the overall SMR after 30 years was 1.6 (95% CI 1.2–2.2) (Olafsson et al., 1998). This risk was most marked in those with remote symptomatic epilepsy (SMR 2.3; 95% CI 1.4–3.5), whereas there was no significantly increased risk in any age group for those with idiopathic epilepsy at any point during follow-up (overall SMR 1.3; 95% CI 0.8–1.9). The overall risk of mortality was elevated for only the first 14 years of follow-up, returning to baseline risk thereafter. The SMR was 3.0 (95% CI 1.5–5.4) at 0–4 years follow-up, 2.1 (95% CI 1.0–3.9) at 5–9 years, 2.0 (95% CI 1.0–3.8) at 10–14 years follow-up, and between 0.7 and 1.2 thereafter.

In the Mayo Clinic Linkage study, a historical cohort of all residents in Rochester, Minnesota who had a first diagnosis of epilepsy between 1935 and 1974, the SMR for the total group after 29 years follow-up was 2.3 (95% CI 1.9–2.6) (Hauser et al., 1980). The SMR was initially high at 3.8 (95% CI 2.8–5.0) at 0–1 years follow-up, subsequently decreasing to 2.4 (95% CI 1.7–3.3) at 2–4 years and SMR 2.0 (95% CI 1.4–2.7) at 5–9 years. The SMR was not significantly elevated at 10–14 years follow-up (SMR 1.4; 95% CI 0.8–2.2), 15–19 years (SMR 1.4; 95% CI 0.7–2.5), and 20–24 years (SMR 1.8; 95% CI 0.7–3.0), but was again significantly increased at 25–29 years follow-up (SMR 3.9; 95% CI 1.8–7.6).

The SMRs by broad etiologic category for these studies are shown in Table 2. The SMR is either not increased, or is slightly increased in people with idiopathic/cryptogenic epilepsy, is between 2.2 and 3.7 for those with symptomatic epilepsy, but is much higher in people with a congenital neurologic deficit. Most studies did not have comparable data for specific causes of death.

Table 2.   Population studies of mortality in people with epilepsy with standardized mortality ratios (with 95% confidence intervals) for the major etiological categories
ReferenceIdiopathic/cryptogenic SMR (95% CI)Acute symptomatic SMR (95% CI)Remote symptomatic SMR (95% CI)Congenital deficit SMR (95% CI)
  1. N/A, Not available.

  2. aAcute and remote symptomatic causes could not be differentiated.

  3. bFourteen of 42 with remote symptomatic seizures had learning disability or cerebral palsy.

  4. cOnly SMRs for the whole cohort and for those without a severe neurologic deficit.

Hauser et al. (1980)a1.8 (1.4–2.3)2.2 (1.8–2.7)11 (6.9–16.4)
Olafsson et al. (1998)b1.3 (0.8–1.9)N/A2.3 (1.4–3.5)N/A
Lhatoo et al. (2001)1.3 (0.9–1.9)3.0 (2.0–4.3)3.7 (2.9–4.6) 25 (5.1–73.1)
Lindsten et al. (2000)1.1 (0.5–2.4)N/A3.3 (2.4–4.5)N/A
Camfield et al. (2002)c 1.51 (0.19–2.83)N/A
Hospital-based studies

The largest hospital-based study was a Swedish study that identified 9,061 people aged 15–97 years who were admitted for inpatient care with a diagnosis of epilepsy between 1980 and 1989 (people with both incident and prevalent epilepsy) (Nilsson et al., 1997). Four thousand and one people in the cohort died. The overall SMR was 3.6 (95% CI 3.5–3.7), highest in young patients but significantly elevated in all age groups. The overall SMR was compared with that in patients who died more than 4 years after entering the cohort and thus at least 4 years after onset of epilepsy. The SMR in the group of patients who died later was 3.1 (95% CI 3.0–3.3), lower than the SMR of the whole cohort but within the same range. No comparison was made of the SMRs for the group of patients who died ≤4 years after entering the cohort and those who died >4 years after entering the cohort.

In a retrospective Scottish study of people attending epilepsy services between 1981 and 2001, those with newly diagnosed epilepsy (N = 890) had a 42% increased risk of premature mortality compared with the general population (SMR 1.42; 95% C.I 1.16– 1.72) (Mohanraj et al., 2006). People who did not respond to treatment had a greater increase in mortality (SMR 2.54; 95% CI 1.83–3.44), whereas people in remission had no increased risk (SMR 0.95; 95% CI 0.68–1.29).

In a Danish study (Henriksson et al., 1970) cited elsewhere, of 2,450 patients with prevalent epilepsy aged 15–89 attending four epilepsy outpatient clinics from 1950–1963, and excluding patients with acute symptomatic causes, the overall SMR for the cohort was 2.8, with male patients having a higher SMR (3.5) than female patients (2.0) (Hauser et al., 1980).

Institutional studies

In a retrospective Dutch study, the mortality of all patients attending an institution (both inpatients and outpatients) between 1953 and 1967 was followed, with a mean follow-up of 28 years (range 6 months to 41 years) (Shackleton et al., 1999). The overall SMR for the cohort with incident epilepsy was 3.2 (95% C.I 2.9–3.5). The SMR was significantly elevated soon after diagnosis (SMR 16; 95% CI 11–20) in the first 2 years, decreasing thereafter to an SMR of approximately 7.0 for the next eight years. The SMR decreased further to 3.9 and subsequently plateaued at between 2.0 and 2.4 between 15 and 34 years. The SMR was no longer significantly elevated in the last years of follow-up (years 35–41: SMR 0.9 [95% CI 0.4–1.4]).

Two studies carried out in institutions for people with mental disorders in the 1930s and 1940s were identified, one from the United States and the other from Sweden (Malzberg, 1934; Alstrom, 1942). Both of these studies comprised patients with learning disability and prevalent epilepsy (Shackleton et al., 2002), and both reported high SMRs: 8.0 (United States) and 8.7 (Sweden).

In a study from the Chalfont Centre for Epilepsy in the United Kingdom, deaths in 2,099 patients with prevalent epilepsy who were admitted between 1931 and 1971 were investigated. Between 1951 and 1977, 636 people died (both at the center and after discharge), giving an SMR of 3.0 (95% CI 2.8–3.3) (White et al., 1979). In another study from the Chalfont Centre, the death certificates of all patients who died between January 1980 and December 1990 were examined; there were 113 deaths giving an SMR of 1.9 (95% CI 1.6–2.3) (Klenerman et al., 1993). The deaths occurring in people still resident in the Chalfont Centre in 5-year periods from 1896–1965 were also examined (O’Donoghue & Sander, 1997). During this period, there were 416 deaths, with an overall SMR of 2.34 (95% CI 2.12–2.56). The SMR remained relatively stable at between 1 and 3 throughout most of the period of follow-up, with the lowest reported SMR (0.91) occurring during the earliest period of observation (1896–1900) and the highest occurring between 1916 and 1920 (4.41), which may in part be explained by the Spanish Flu pandemic preferentially affecting death rates in institutions.

Population-based mortality trends in people with epilepsy

Mortality rates (age-adjusted mortality rates per million) per year from all causes in 10 developed countries (Australia, Canada, England & Wales, France, Germany, Italy, Japan, The Netherlands, Spain, and the United States) were studied between 1979 and 1997 to determine if there were any changing patterns in neurologic deaths (Pritchard et al., 2004). Although there were significant differences in the annual mortality rates between different countries, ranging from 6 per million in Japan to 24 per million in France, there was little variation in mortality rates year by year in each country. Males had a consistently higher mortality rate than females in all countries.

The trends in annual mortality rates (and hospital admissions) in England and Wales between 1993 and 2000 were examined using ICD-9 coding for death certificates (Bruce et al., 2004). Epilepsy was listed in about 2,000 death certificates and listed as the underlying cause of death in approximately 800 cases each year. Overall there were 15,990 death certificates where epilepsy was mentioned and 6,497 (40.6%) in which it was listed as the underlying cause of death. Age-standardized annual death rates for epilepsy varied little between 1993 and 2000. Deaths were higher in males for each year, with a mean of 484 deaths attributable to epilepsy each year (compared with 332 in females). Males had higher annual mortality rates than females for all age groups. In both males and females there was a sharp increase in mention of epilepsy in the elderly.

The mortality rates (per million person-years) of people with epilepsy between 1950 and 1994 in England and Wales and the United States were analyzed (O’Callaghan et al., 2000). Trends were broadly similar for both countries, with mortality consistently higher among males, although mortality rates were higher in England and Wales than in the United States. The mortality rate declined in both countries between birth and the age of 10, increasing sharply during teenage years and early adulthood. Rates fell gradually thereafter until the age of 70, when they increased, with the increase in mortality in those aged >70 years being more pronounced in England and Wales. There was evidence of significantly decreased mortality rates in successive birth cohorts born after 1950; this decrease occurred earlier among women (after 1905) but was more marked after 1950. Similarly the age distribution of those who died also changed between 1950 and 1994 with a two- to threefold decrease in mortality in young people, a decrease in young and middle-aged adults (with some differences between the countries), and a steep decrease in the elderly between 1950 and 1970 but an increase thereafter (O’Callaghan et al., 2000). There was little evidence of period effects. Mortality was highest during the 1950s, decreased slightly until the 1970s, and remained relatively stable thereafter in the United States, while increasing slightly in England and Wales after 1980 (O’Callaghan et al., 2000).

An earlier study (Massey & Schoenberg, 1985), which compared mortality rates in 33 countries between 1967 and 1973 with the mortality rates for the same countries in the 1950s (Goldberg & Kurland, 1962), found a significant decrease in mortality rates for most countries.

Discussion

  1. Top of page
  2. Summary
  3. Aims
  4. Methodology
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

An attempt was made to address two issues: (1) how SMRs change in people with epilepsy during the course of the condition and (2) how reported mortality rates (and SMRs) in people with epilepsy have changed over time.

SMRs

SMRs compare the mortality rates in people with epilepsy with that of the population from which they derive and hence give some indication of the premature mortality experienced by them. In examining reported SMRs in prevalent cohorts, it needs to be emphasised that prevalence studies generally overrepresent people with more severe forms of epilepsy, while simultaneously missing some people that may have died previously for whatever reason. It is likely, therefore, that results from incident cohorts provide a more accurate picture. Currently, there are few incident cohorts available for comparison.

The risk of premature mortality is significantly higher than that of the general population in the initial 1–2 years following seizure onset, and this risk decreases thereafter (Hauser et al., 1980; Cockerell et al., 1994; Loiseau et al., 1999). Much of this initial risk is related to the underlying etiology and seizure type as seen in the Gironde study (Loiseau et al., 1999) and the Canadian pediatric study (Camfield et al., 2002). The SMR in children is proportionally higher due to the lower expected death rate in children (Camfield et al., 2002).

The SMR has been consistently shown to decease thereafter, often with death rates comparable with those of the general population (Hauser et al., 1980; Cockerell et al., 1994; Olafsson et al., 1998). There is a suggestion, however, from several studies that there is a subsequent late increase in mortality ratio after 10 years (Lindsten et al., 2000; Lhatoo et al., 2001; Camfield et al., 2002) or later (Hauser et al., 1980). In contrast, no such late increase in mortality was observed in the Icelandic study (Olafsson et al., 1998). This temporal mortality trend appears to be significant only among people with symptomatic epilepsy. An analysis of those people classified as having idiopathic/cryptogenic epilepsy in the NGPSE showed that the SMR was not significantly increased at any point during follow-up (Lhatoo et al., 2001) as was also found in the Iceland study (Olafsson et al., 1998).

If such a late increase in mortality risk does occur, it raises the question as to why this should occur and in particular questions the impact of treatment (medical and surgical). In the NGPSE and the Mayo Clinic cohorts, there is evidence that the SMR was significantly high at last follow-up despite the fact that approximately 70% in both cohorts had entered terminal remission. The assertion that treatment lowers the mortality risk rests upon the assumption that the majority of people with epilepsy die from epilepsy related causes. Although it is undoubtedly true that rendering patients with severe epilepsy seizure-free either by surgery (Sperling et al., 1999; Bell et al., 2010) or by medication in patients with remote symptomatic epilepsy (Strauss et al., 2003) reduces the mortality rate, it is less clear that treatment affects the mortality rate in people with mild or idiopathic epilepsy. The majority of people with epilepsy in general-population cohorts die from non–epilepsy-related causes (Bell et al., 2004; Lhatoo & Sander, 2005).

The second question regarding mortality is whether reported rates have changed over time. Although comparing SMRs from similar source populations is undoubtedly crude, it demonstrates no significant differences in ratios in studies from the 1930s to the 1990s (Shackleton et al., 2002). This was shown in a study looking at 5-year SMRs from the same institution between 1895 and the 1960s, where no significant differences were noted (O’Donoghue & Sander, 1997).

Mortality rates

Mortality rates are usually age standardized and are typically expressed as the number of deaths/100,000/year. They enable us to give an indication of how death in people with epilepsy varies over time.

Population-wide studies are largely based on death certificate data (Massey & Schoenberg, 1985; O’Callaghan et al., 2000; Goldacre et al., 2003; Bruce et al., 2004; Pritchard et al., 2004; Goldacre et al., 2010). Although it is well recognized that mortality statistics based on death certificates significantly underestimate mortality rates in people with epilepsy (Bell et al., 2004; Bruce et al., 2004), such deficiencies should not bias interpretation of secular trends unless there is evidence that the degree of underreporting varies over time (O’Callaghan et al., 2000).

The study comparing epilepsy mortality rates (per million patient-years) in the United States and England and Wales demonstrates a significant birth cohort effect with progressively lower mortality rates in children and young people, which is likely to be as a result of improved perinatal care (O’Callaghan et al., 2000). This is supported by evidence from population studies, which suggest that the incidence of epilepsy is decreasing in children (Kurtz et al., 1998; Sillanpaa et al., 2006). The apparent decrease in mortality rates shown in the study comparing rates in 33 countries about 20 years apart (Massey & Schoenberg, 1985) may represent an age-specific effect, with the decreased mortality rates reflecting the decreasing mortality rate in children mirrored by the falling incidence of epilepsy in children. There are also methodologic differences between the two studies. In contrast there is no evidence that the mortality rates from epilepsy have decreased since the 1970s (Hauser et al., 1980; O’Callaghan et al., 2000; Bruce et al., 2004; Pritchard et al., 2004; Goldacre et al., 2010).

Most of the population studies provide mortality rates in people with epilepsy up to the 1990s and so do not include many people taking the new antiepileptic drugs (AEDs). One study (Goldacre et al., 2010) does, however, examine mortality in England between 1996 and 2006 with no significant change in mortality rates in people with epilepsy during this time. The impact of the new AEDs in reducing mortality is, therefore, unclear and further studies are needed. Over the last decade, certifying physicians have been encouraged to mention epilepsy and, where appropriate, SUDEP on death certificates, following the finding that previously epilepsy was frequently not included even in death certificates of people who had active epilepsy (Hanna et al., 2002). If this encouragement was heeded one would expect that the number of deaths attributed to epilepsy would have increased. This does not appear to be the case (Goldacre et al., 2010), suggesting the possibility that the actual number of deaths may have fallen, although no firm data are available to support this.

Acknowledgments

  1. Top of page
  2. Summary
  3. Aims
  4. Methodology
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

This work was carried out at University College London Hospitals/University College London, which received a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme. It was supported by the UK National Society for Epilepsy and the Brain Research Trust. JWS is partly supported by the Dr Marvin Weil Epilepsy Research Fund.

Disclosure

  1. Top of page
  2. Summary
  3. Aims
  4. Methodology
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. None of the authors has any conflicts of interest in relation to this work to disclose.

References

  1. Top of page
  2. Summary
  3. Aims
  4. Methodology
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References