Aidan Neligan

The long-term risk of premature mortality in people with epilepsy

People with epilepsy have an increased risk of premature death. The risk is highest soon after onset of seizures. We report the findings of a long-term follow-up population-based study of people with epilepsy with regards to premature mortality. The National General Practice Study of Epilepsy is a prospective study flagged at the National Health Service Information Centre in the UK. Over 1000 people with new onset seizures were followed from the mid 1980s until April 2009. Of these, 564 people were classified at 6 months as having definite epileptic seizures, 228 as having possible epileptic seizures and 220 as having febrile seizures. The remainder were excluded (n=104 because of an unknown prior diagnosis of epilepsy or neonatal seizures) or classified as not having epilepsy (n=79). At median follow-up of 22.8 years there had been 301 deaths in the cohort; 300 of these were in people with definite or possible seizures. Death certificates were obtained for all but three of those who died. The overall standardized mortality ratio for those with definite or possible epilepsy was 2.2 (95% confidence interval 1.97-2.47), and was higher in those with definite seizures (2.6). In those who were alive at 20 years follow-up, the standardized mortality ratio in the subsequent years remained significantly elevated (2.2, 95% confidence interval 1.6-3.2). Pneumonia (standardized mortality ratio 6.6, 95% confidence incidence 5.1, 8.4) was a common cause of death with a consistently elevated standardized mortality ratio throughout follow-up. The standardized mortality ratio for ischaemic heart disease was significantly elevated for the first time in the last 5 years of follow-up (3.3, 95% confidence interval 1.6-7.0). Few people died from epilepsy-related causes. The risk of premature death remains significantly elevated at 20-25 years after the index seizure despite most of the cohort being in terminal remission (defined as 5 years or more seizure-free, on or off anti-epileptic medication) at the last follow-up. Further studies are needed to explore the reasons for this long-term increase in premature mortality.

Frequency and Prognosis of Convulsive Status Epilepticus of Different Causes: A Systematic Review

We conducted a systematic review of all studies of status epilepticus (SE) with more than 30 patients published between January 1, 1990, and December 31, 2008, to determine the frequencies of the common underlying causes and the extent to which the underlying causes affect the prognosis of an episode of SE. The frequencies of underlying causes vary among studies and show marked geographic differences, but in most studies, the most common underlying causes were cerebrovascular disease and low antiepileptic drug levels. A relatively good prognosis of SE is found when the underlying cause is associated with low antiepileptic drug levels or alcohol abuse, and a relatively poor outcome occurs when the underlying cause is cerebrovascular disease, particularly in the case of SE due to acute cerebral anoxia, but in most conditions, the reported prognosis is variable. Also, when SE occurs in the context of an acute cerebral insult, such as cerebral infection or cerebrovascular disease, the prognosis of the acute cerebral event is worsened.

Prognostic factors, morbidity and mortality in tonic-clonic status epilepticus: a review.

OBJECTIVES to determine how the duration of SE, the EEG findings during/after SE, the depth of coma at presentation and age impact on the prognosis of convulsive status epilepticus indepedent of aetiology and to analyse the outcome of status epilepticus with respect to mortality and morbidity (the latter measured in terms of functional decline, cognitive/intellectual decline and the prospective risk of epilepsy). DESIGN a systematic review of all studies of status epilepticus (SE) with greater then 30 patients published from the 01/01/1990 up until 31/12/2009. RESULTS oveall the longer the duration of SE the worse the prognosis particularly after 1-2h of continuous seizures although this affect may be lost after 10h. The depth of coma correlates well with outcome. Only periodic epileptiform discharges (PEDs) have been shown to be associated with a poorer outcome in most (but not all) studies although this is probably related to the underlying aetiology. Age is an important prognostic factor with children having a better prognosis then adults. CONCLUSIONS age and depth of coma at presentation appear to be the strongest predictors of outcome of SE independent of aetiology with the duration of SE and the EEG findings less important.

Temporal trends in the mortality of people with epilepsy: a review.

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.

An unknown quantity-The worldwide prevalence of epilepsy

The reported incidence (rate of new cases in a population) of epilepsy is consistently lower in high‐income than in lower‐income economies, whereas opinions vary regarding comparative prevalence rates (proportion of the population with epilepsy). For any condition that does not influence mortality, lifetime prevalence should approximate to the cumulative incidence. We suspected that epilepsy prevalence might be uniform throughout the world, whereas incidence is higher in resource‐poor countries. To test whether our suspicion was reasonable, we conducted a Medline search to estimate the prevalence of active and lifetime epilepsy in different economic areas throughout the world. We found that the range of estimated prevalence of epilepsy may be broadly similar throughout the world, but comparison is limited by lack of door‐to‐door studies in high‐income economies and by variations in the definitions of active epilepsy. We contend that any inconsistencies between incidence and prevalence are due largely to the excess premature death rate in people with epilepsy in lower‐income economies. Much of the variability in epidemiologic indices arises from differences in study methodology, definitions, and risk factors. The epidemiology of epilepsy, and particularly its mortality, needs thorough investigation using uniform definitions that do not include antiepileptic drug use; causes of death should be identified and actions, including treatment and education, should be taken to avoid preventable deaths.

The epidemiology of the epilepsies.

Abstract This chapter provides an overview of some aspects of the epidemiology of epilepsy, in particular the incidence and prevalence, prognosis, and mortality. There are a number of methodological difficulties when attempting to apply standard epidemiological processes to a symptom complex such as epilepsy, and these are touched upon. Incidence and prevalence studies in developed and resource-poor settings are reviewed and the changing profile of age-specific incidence of epilepsy is discussed. The prognosis in relation to probabilities of seizure recurrence after single and recurrent seizures, the risk of relapse after antiepileptic drug withdrawal and of the untreated condition are covered. Outcome of epilepsy surgery is reviewed. The data on the largely neglected area of prognosis in treatment-resistant epilepsy are summarized. Evidence for the risk of premature death in people following a first seizure and in people with epilepsy in population-based incident cohorts is reviewed with a discussion of causation and the relative frequency of epilepsy-related and nonepilepsy-related deaths

Long-term risk of developing epilepsy after febrile seizures A prospective cohort study

Objective: We report the prospective follow-up of a cohort of people from the onset of febrile seizures for a median of 24 years to estimate the long-term risk of developing epilepsy. Methods: The National General Practice Study of Epilepsy is a large prospective community study of 1,195 people with a first suspected seizure followed from the 1980s, of whom 220 (18%) had febrile seizures. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for subsequent epilepsy were calculated in 5-year age bands. Results: Follow-up information was obtained for 181 (83%) people with a mean follow-up for the whole cohort of 21.6 (SD 6.0) years. Of these, 175 (97%) were seizure-free in the preceding 5 years, whereas 171 (94%) were seizure-free and off antiepileptic drugs. Six percent developed epilepsy, but the risk of developing epilepsy in the cohort over the whole follow-up period was almost 10 times that of the general population (SIR 9.7, 95% CI 5.7–16.4). The SIR was significantly elevated in the 0- to 14-year age groups but not in the 15- to 19-year age group (SIR 4.5, 95% CI 0.6–32.1). Conclusion: The risk of developing epilepsy in people who had febrile seizures seems to decrease with time. Further long-term studies are needed to confirm this.

A survey of adult and pediatric epilepsy surgery in the United Kingdom

All consultant epilepsy neurosurgeons were asked to prospectively record all epilepsy surgery procedures carried out at their center between April 2010 and March 2011. Figures were compared to a previous survey completed in 2000. Of a total of 710 procedures, temporal lobe surgery was the most common resective surgery. Although extratemporal lesional surgery was less common, vagus nerve stimulator (VNS) implantation accounted for almost half the procedures. The numbers for all surgical procedures, with the exception of VNS implantations, had decreased. This decrease may represent a global rather than a regional phenomenon. Further longitudinal multinational data on epilepsy surgery is required to confirm or refute this theory.

How refractory is refractory epilepsy? Patterns of relapse and remission in people with refractory epilepsy

BACKGROUND Outcome studies in people with epilepsy have largely focused on the prognosis in the early stages and factors predictive of early remission. Few studies have examined prognosis in chronic refractory epilepsy. METHODS We determined the pattern of remission and relapse of epilepsy in a cohort of people with refractory epilepsy (seizures in the past two years, at least five years after onset and who have been treated with at least 2 appropriate antiepileptic drugs during that time) to investigate whether any clinical or demographic features are predictive of seizure patterns. Seizure patterns were defined as intermittent (at least one previous period of remission of two or more years with a subsequent relapse) or continuous (no periods of remission of two years or more since seizure onset). We correlated clinical variables with these patterns. We devised a prognostic model summarising patterns of remission and relapse over time in epilepsy. RESULTS 290 people were recruited, of whom 70% had a continuous pattern of seizures with the remaining 30% having an intermittent pattern. The only clinical variables which significantly differed between the two groups were a higher total number of antiepileptic drugs taken by those in the continuous group (P=0.01) and fewer seizures in the previous year in the intermittent group (P<0.001). A prognostic model of epilepsy is proposed. CONCLUSION There is considerable heterogeneity in long-term seizure patterns in people who do not enter long-term remission in the early years after diagnosis.

Treatment changes in a cohort of people with apparently drug-resistant epilepsy: an extended follow-up

Background The seizure response to the addition of a previously unused antiepileptic drug in a cohort of 155 people with refractory epilepsy was previously reported after a median of 18 months follow-up. Methods The authors followed 139 (90%) of the original cohort for a median follow-up of 6.9 years to determine the longer term outcome in people with refractory epilepsy. Results During the 6.9 year follow-up period, a total of 448 medication changes were made. Eight per cent of these resulted in 12 months or more of seizure freedom and a further 17% of changes resulted in at least 50% improvement in seizure frequency. At the last follow-up, 26 (19%) of individuals had been seizure-free for 12 months or more, and 41 (29%) had 50%–99% improvement in seizure frequency. Terminal seizure freedom was correlated with having no seizures at the time of the previous report (p=0.03), a lower number of previous antiepileptic drugs taken (p=0.052) and a lower number of concomitant antiepileptic drugs (p=0.03). In those who entered remission the probability of remaining seizure-free 5 years later was 0.48 (95% CI 0.32 to 0.63). Discussion This suggests that about half of people with apparent drug-resistant epilepsy can have significant improvements in seizure control with further drug changes. Some will subsequently relapse, but long periods of seizure freedom or significantly improved seizure control in the absence of complete seizure control can occur. Such valuable improvements suggest that the recently proposed International League against Epilepsy definition of refractory epilepsy may be too restrictive.