Dm Goodridge

Mortality from epilepsy : results from a prospective population-based study

Patients with epilepsy may be subject to an increased risk of premature death from the underlying cause, or from the epilepsy itself. The extent and nature of this risk has been insufficiently investigated. Standard mortality ratios (SMRs) of patients with newly diagnosed epilepsy were determined in a prospective national population-based study. 1091 patients with newly diagnosed or suspected epilepsy were ascertained who were attending one of 275 UK general practices from 1984-1987. 1091 patients were classified after 6 months as definite epilepsy (564), possible epilepsy (228), febrile seizures (220), or not epilepsy (79). Over a median follow up of 6.9 years the SMR for patients with definite or possible epilepsy was 2.5 (95% CI 2.1-2.9), and 3.0 (2.5-3.7) for definite epilepsy. The SMR was highest during the first year after diagnosis 5.1 (3.8-6.5), declined to 2.5 (1.5-3.9) at 3 years, and 1.3 (0.7-2.0) at 5 years. The commonest causes of death were pneumonia (SMR 7.2), cancer (3.5), and stroke (3.7). The SMR for patients with idiopathic epilepsy was 1.6 (1.0-2.4), remote symptomatic epilepsy 4.3 (3.3-5.5), and acute symptomatic epilepsy 2.9 (1.7-4.5). Mortality in patients with newly-diagnosed epilepsy was high, mainly due to the underlying cause. The SMR for idiopathic epilepsy was also raised, suggesting that epilepsy per se may carry a small risk of death.

Mortality in epilepsy in the first 11 to 14 years after diagnosis: Multivariate analysis of a long-term, prospective, population-based cohort

The United Kingdom National General Practice Study of Epilepsy is a prospective, population‐based study of newly diagnosed epilepsy. A cohort of 792 patients has now been followed for up to 14 years (median follow‐up [25th, 75th percentiles] 11.8 years, range 10.6–11.7 years), a total of 11,400 person‐years. These data are sufficient for a detailed analysis of mortality in this early phase of epilepsy. Over 70% of patients in this cohort have developed lasting remission from seizures, although the mortality rate in the long term was still twice that of the general population. The standardized mortality ratio (SMR), the number of observed deaths per number of expected deaths, was 2.1 (95% confidence interval [CI] = 1.8, 2.4). Patients with acute symptomatic epilepsy (SMR 3.0; 95% CI = 2.0, 4.3), remote symptomatic epilepsy (SMR 3.7; 95% CI = 2.9, 4.6), and epilepsy due to congenital neurological deficits (SMR 25; 95% CI = 5.1, 73.1) had significantly increased long‐term mortality rates, whereas patients with idiopathic epilepsy did not (SMR 1.3; 95% CI = 0.9, 1.9). This increase in mortality rate was noted particularly in the first few years after diagnosis. Multivariate Cox regression and time‐dependent co‐variate analyses were utilized for the first time in a prospective study of mortality in epilepsy. The former showed that patients with generalized tonic‐clonic seizures had an increased risk of mortality. The hazard ratio (HR), or risk of mortality in a particular group with a particular risk factor compared to another group without that particular risk factor, was 6.2 (95% CI = 1.4, 27.7; p = 0.049). Cerebrovascular disease (HR 2.4; 95% CI = 1.7, 3.4; p < 0.0001), central nervous system tumor (HR 12.0; 95% CI = 7.9, 18.2; p < 0.0001), alcohol (HR 2.9; 95% CI = 1.5, 5.7; p = 0.004), and congenital neurological deficits (HR 10.9; 95% CI = 3.2, 36.1; p = 0.003) as causes for epilepsy and older age at index seizure (HR 1.9; 95% CI = 1.7,2.0; p < 0.0001) were also associated with significantly increased mortality rates. These hazard ratios suggest that epilepsy due to congenital neurological deficits may carry almost the same risk of mortality as epilepsy due to central nervous system tumors and that epileptic seizures subsequent to alcohol abuse may carry almost the same risk of mortality as epilepsy due to cerebrovascular disease. The occurrence of one or more seizures before the index seizure (the seizure that led to the diagnosis of epilepsy and enrolment in the study) was associated with a significantly reduced mortality rate (HR 0.57; 95% CI = 0.42, 0.76; p = 0.00001). Time‐dependent co‐variate analysis was used to examine the influence of ongoing factors, such as seizure recurrence, remission, and antiepileptic drug use, on mortality rates in the cohort. Seizure recurrence (HR 1.30; 95% CI = 0.84, 2.01) and antiepileptic drug treatment (HR 0.97; 95% CI = 0.67, 1.38) did not influence mortality rate. There were only 5 epilepsy‐related deaths (1 each of sudden unexpected death in epilepsy, status epilepticus, burns, drowning, and cervical fracture), suggesting that death directly due to epileptic seizures is uncommon in a population‐based cohort with epilepsy. Ann Neurol 2001;49:336–344

Factors predicting prognosis of epilepsy after presentation with seizures

The objective of this study was to identify the factors, at the time of diagnosis, that determine the prognosis for remission of epilepsy. A prospective community‐based cohort study of 792 patients recruited at the time of their first diagnosis of epileptic seizures was undertaken; in those classified 6 months after presentation, the median follow‐up period was 7.2 years (quartiles at 6.2 and 8.2 years) after presentation. We analyzed data from 6 months after the first identified seizure, which prompted the dianosis of epilepsy, to allow us to factor in those aspects contingent on a diagnostic assessment. Baseline clinical and demographic data were analyzed using the Cox proportional hazards regression model with remission of epilepsy for 1, 2, 3, and 5 years as outcome measures. The dominant clinical feature predicting remission was the number of seizures in the 6‐month diagnostic assessment period. Thus, the chance of entering 1 year of remission by 6 years for a patient who had 2 seizures during this initial 6 months was 95%; for 5 years of remission, it was 47% as opposed to 75% for 1 year of remission and 24% for 5 years of remission if there had been 10 or more seizures during this period. The number of seizures in the early phase of epilepsy (here, taken as the first 6 months after presentation) is the single most important predictive factor for both early and long‐term remission of seizures. Ann Neurol 2000;48:833–841

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.

Epilepsy in a population of 6000 re-examined: secular trends in first attendance rates, prevalence, and prognosis.

It is important to document changes in the vital statistics of epilepsy in the general population so that the success or failure of prevention and treatment can be assessed and health provisions planned. A population of 6000 persons was studied 10 years apart to determine secular trends in the prevalence and prognosis of epilepsy. The lifetime prevalence of all patients with one or more afebrile seizures was 20.3/1000 (95% CI 16.9-24.3) in 1983 and 21.0/1000 (95% CI 17.6-25.1) in 1993. The prevalence of active epilepsy was 5.3/1000 (95% CI 3.6-7.5) in 1983 and 4.3 (95% CI 2.8-6.3) in 1993. To assess trends in incidence rates the annual first attendance rates were measured from 1964 to 1993. Annual first attendance rates in children (age < 20 years) have declined from 152.4/100,000 (90% CI 106.0-212.9) in the years 1974-83, to 60.9/100,000 (90% CI 33.0-103.3) in the years from 1984-93, suggesting that the incidence of epilepsy in children is falling. Also noteworthy was the first attendance rates for epilepsy in elderly people (61-80 years) in the years 1984-93, of 82.0 (90% CI 38.5-154.0), higher than in any other age group. This increase in the number of elderly patients with epilepsy is important, and has health planning implications, especially with the overall increase in the total elderly population. There was, however, no evidence that prognosis has significantly altered in the past 40 years.

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.

Neurological Disease in a Defined Population: The Results of a Pilot Study in Two General Practices

A pilot study was set up to ascertain incident neurological disorders occurring in 25,000 people attending two general-practice surgeries for a period of 1 year. To achieve completeness of ascertainment and diagnostic validity poses considerable logistical and theoretical difficulties, and these are discussed. The commonest disorders (incidence in parentheses) were headaches (210/100,000), back syndromes (319/100,000), acute cerebrovascular disease (128/100,000), and migraine (64/100,000), with non-specific symptoms the most common problem overall (514/100,000). The incidence of Parkinsons disease was 26/100,000 and that of epilepsy 23/100,000. The pilot study will form the basis for a more comprehensive linkage scheme between the National Hospital for Neurology and Neurosurgery in London and surrounding general practices with a total base population of 100,000.

Outcome of seizures in the general population after 25 years: a prospective follow-up, observational cohort study

Objectives We investigated long-term (to 25 years) seizure prognosis and survival in people with newly diagnosed epilepsy in the community. We explored whether prognosis is different in those with epilepsy (>2 unprovoked seizures) and those with a single seizure at presentation. Methods This is a prospective observational cohort study of people with newly diagnosed seizures. We investigated seizure outcome and survival in people presenting with a single seizure and in those presenting with >2 seizures (epilepsy). Results 695 people (median follow-up 23.6 years) had unprovoked epileptic seizures. For seizure analysis we excluded 38 people with missing data leaving 657 (309 male, and 249 aged <18 years). Seizures recurred in 67%. The 354 people with epilepsy were only slightly more likely to have further seizure recurrence than the 302 people with a single seizure at presentation (HR 1.32, 95% CI 1.09 to 1.59). In 327 people with complete follow-up, 268 (82%, 95% CI 77% to 86%) were in terminal remission; (80%, (95% CI 73% to 85%) in those with epilepsy at presentation). Premature mortality was increased in people with epilepsy (standardised mortality ratio 1.67; 95% CI 1.40 to 1.99) and those with a single seizure at presentation (standardised mortality ratio 2.65; 95% CI 2.23 to 3.15). It is also high in those with early remission. Conclusions People with epilepsy and with single seizures at presentation in the community generally have good prognosis for seizure control with prolonged follow-up. The risk of premature mortality is significantly increased in both groups.

The contribution of British general practice to our knowledge of epilepsy and its effects on people

INTRODUCTION British general practice is a good base for epidemiological research which is evidenced by the study of epilepsy. SOURCES OF DATA A comprehensive search of PubMed using various keywords for articles on epilepsy research performed in British general practice. AREAS OF AGREEMENT Studies in the setting of general practice have contributed significantly to knowledge in the field of epilepsy, especially in relation to epidemiology, studies of prognosis and treatment patterns and psychosocial aspects. AREAS OF CONTROVERSY The extent to which epilepsy can be managed in general practice. GROWING POINTS The importance of primary care research and the importance of collaborative studies between general practice, hospital and university departments. AREAS TIMELY FOR DEVELOPING RESEARCH The effects of interventions at general practice level on seizure control, morbidity and mortality.