[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
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.
[Show abstract][Hide abstract] ABSTRACT: People with epilepsy are known to be at increased risk of death by drowning but there are few data available regarding the size of the risk. We aimed to quantify the risk using meta-analysis.
A literature search identified 51 cohorts of people with epilepsy in whom the number of deaths by drowning in people with epilepsy and the number of person-years at risk could be estimated. Population data were taken from the WHO Statistical Information Service or from the UK Office for National Statistics where available. Standardized mortality ratios (SMRs) with 95% CIs were calculated for each cohort, for groups of cohorts, and for the total population. Additionally, an SMR for drowning in people with epilepsy in England and Wales (1999-2000) was calculated using National Registries.
Eighty-eight drowning deaths were observed compared with 4.70 expected, giving an SMR of 18.7 (95% CI 15.0 to 23.1). Compared with community-based incident studies (SMR 5.4), the SMR was significantly raised in prevalent epilepsy (SMR 18.0), in people with epilepsy and learning disability (SMR 25.7), in those in institutional care (SMR 96.9), and in those who had a temporal lobe excision (SMR 41.1). The SMR for people with epilepsy in England and Wales was 15.3.
The risk of drowning in people with epilepsy is raised 15- to 19-fold compared with people in the general population. It is important that people with epilepsy and their carers be informed of these risks so that deaths can be prevented.
[Show abstract][Hide abstract] ABSTRACT: Death certificates are an unreliable source of information on cause of death, and mortality due to epilepsy can thus be underestimated.
We investigated people with epilepsy who had died, and attempted to identify factors that influence inclusion of epilepsy on the death certificate; eight factors were hypothesised and entered into a univariate logistic regression model.
Epilepsy was on the death certificate of 16/243 (7%) people who had had epilepsy. Factors that influenced whether or not epilepsy appeared on the certificate were seizure frequency, antiepileptic drug treatment, cause of death, and certifying physician. Factors that did not seem to influence the inclusion of epilepsy were presence of convulsive seizures, occurrence of seizures during follow up, and age at death.
We have estimated the degree of unreliability of death certificates (as currently used in the UK) as a source of information on cause of death in epilepsy. We have found that epilepsy may not appear on death certificates even if people had active epilepsy.
[Show abstract][Hide abstract] ABSTRACT: Women with epilepsy have different needs from men, particularly associated with childbearing. Despite clinical guidelines, the care of women with epilepsy remains suboptimal. The aim of this study was to establish whether women with epilepsy recall being given information on topics relating to childbearing. Design of study and methods included a postal questionnaire study of 795 women with epilepsy and of childbearing age. The respondents were identified through both general practices and hospital clinics as part of the Clinical Standards Advisory Group study into Epilepsy Services. Of those women who considered the questions personally relevant, 38-48% recalled receiving information about contraception, pre-pregnancy planning, folic acid and teratogenicity, with lower overall proportions among adolescent women. The proportions that recalled receiving information about vitamin K, safety in child-care and breast-feeding were lower at 12, 24 and 24%, respectively. While it is recognised that information provided may not be recalled, our results suggest that further measures are required to improve the effectiveness of information provision in the UK in relation to women of childbearing age with epilepsy.
Epilepsy Research 01/2003; 52(2):139-46. · 2.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Annals of Neurology 03/2001; 49(3):336-44. · 11.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 diagnosis 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.
Annals of Neurology 01/2001; 48(6):833-41. · 11.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a 12-year follow-up study of children with febrile convulsions (FCs). The National General Practice Study of Epilepsy (NGPSE) is a large prospective community-based cohort study of 1,195 patients of all ages from first presentation with an identified seizure. Two hundred and twenty children with a first febrile convulsion were identified from the above study between 1984 and 1987. Children were prospectively followed up to ascertain subsequent seizures, neurological problems and treatment. Two hundred and seven patients were followed for a minimum of 8.4 years (median 11.2 years). In the FC cohort, 6% of the children developed subsequent epilepsy, which compares with a population risk of about 1.4%. Ten percent had neurological sequelae. Eleven percent of the children had received medication to prevent recurrence of FC, and in one third of these cases, this was for simple FCs. Using a time-dependent covariate Cox proportional hazards model, the number of FCs was associated with an increased risk of epilepsy (hazard ratio 2.48; 95% confidence limits, CL 1.68, 3.65) up to a limit of 4. A statistically significant association between occurrence of complex FC and subsequent epilepsy was not found, but a review of other studies quantified the odds ratio for epilepsy after a complex first FC as 3.4 (95% CL 2.1, 5.4). Epilepsy is a significant if infrequent sequel to FCs. Factors associated with subsequent epilepsy are the number of FCs or a complex first FC. Overtreatment of this condition continues.
European Neurology 02/1999; 41(4):179-86. · 1.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The use of phenobarbital for childhood epilepsy is controversial because of reported behavioural side-effects; however, whether this research can validly be extrapolated to developing countries is not clear. We undertook a randomised comparison of phenobarbital and phenytoin to assess the acceptability and efficacy of phenobarbital as monotherapy for childhood epilepsy in rural India.
Between August, 1995, and February, 1996, 109 unselected children aged 2-18 years with partial and generalised tonic-clonic epilepsy were identified by population screening. 15 families declined to take part. 94 children were randomly allocated treatment with phenobarbital (1.5 mg/kg daily for 2 weeks; maintenance dose 3.0 mg/kg daily; n = 47) or phenytoin (2.5 mg/kg daily then 5.0 mg/kg daily; n = 47). Children were followed up for 12 months. The primary outcome measure was the frequency of behavioural side-effects; behaviour was assessed by the Conners parent rating scale for children aged 6 years and older, and by the preschool behaviour screening questionnaire (BSQ) for those aged 2-5 years, at 12 months or at withdrawal from treatment. Analysis was by intention to treat.
The mean log-transformed scores on the behaviour rating scales did not differ significantly between the phenobarbital and phenytoin groups (Conners 2.64 [SD 0.71] vs 2.65 [0.89], p = 0.97; n = 32 in each group: BSQ 2.12 [1.31] vs 2.18 [1.02], p = 0.94; n = 4 vs 3). The odds ratio for behavioural problems (phenobarbital vs phenytoin) was 0.51 (95% CI 0.16-1.59). There was no excess in parental reports of side-effects for phenobarbital. We found no difference in efficacy between the study drugs (adjusted hazard ratio for time to first seizure from randomisation 0.97 [0.28-3.30]).
This evidence supports the acceptability of phenobarbital as a first-line drug for childhood epilepsy in rural settings in developing countries.
The Lancet 02/1998; 351(9095):19-23. · 39.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To understand the prognosis of newly diagnosed epilepsy to provide rational therapy and advice for patients and their physicians.
The National General Practice Study of Epilepsy (NGPSE) is the first large population-based study that has assessed the prognosis of patients with newly diagnosed epilepsy prospectively over a prolonged period. We review the previously published data on the prognosis of epilepsy after 9 years of follow-up. One thousand ninety-one patients with newly diagnosed or suspected epilepsy who were attending 1 of 275 general practices throughout the United Kingdom between 1984 and 1987 were ascertained. Cases in this study were defined as the occurrence of one or more seizures, including provoked seizures. Prognosis in terms of remission of seizures, and mortality, was analyzed in the patients who were classified 6 months after recruitment as having definite epilepsy (n = 564) or possible/probable epilepsy (n = 228).
Only 33 patients were completely lost to follow-up. After 9 years, 86% [95% confidence interval (CI) 81, 90] of patients with definite epilepsy had achieved a remission of 3 years, and 68% (CI 61, 75), had achieved a remission of 5 years. For the complete cohort, with possible/probable epilepsy included, the rates increased to 87% (CI 83, 91) for 3-year remission and 71% (CI 65, 77) for 5-year remission. The proportion of patients with definite epilepsy who were still in remission at 9-year follow-up (terminal remission) was 68% (CI 62, 74) for 3-year remission and 54% (CI 48, 60) for 5-year remission. When stratified by etiology, the proportions achieving 5-year remission by 9 years was 69% (CI 60, 77) for idiopathic seizures, and 61% (CI 46, 75) for remote symptomatic epilepsy. Age and seizure type had small effects on the chances of achieving remission, with children experiencing slightly lower rates than older patients, and partial seizures having lower remission rates than generalized seizures. The overall standardized mortality ratio (SMR) for patients with definite or possible/probable epilepsy was 2.5 (CI 2.1, 2.9), and 3.0 (CI 2.5, 3.7) for patients who were classified as having definite epilepsy. The SMR for patients with idiopathic epilepsy was 1.6 (CI 1.0, 2.4), for those with remote symptomatic epilepsy it was 4.3 (CI 3.3, 5.5), and for those with acute symptomatic epilepsy it was 2.9 (CI 1.7, 4.5).
Overall, most patients with epilepsy will enter remission; however, there is a higher than expected risk of death, especially in those with symptomatic epilepsy.
[Show abstract][Hide abstract] ABSTRACT: The medical treatment of childhood epilepsy is largely influenced by clinical trials in adult patients. We know of only one randomised comparative trial (of two drugs) in newly diagnosed childhood epilepsy. We have undertaken a long-term, prospective, randomised, unmasked, pragmatic trial of the comparative efficacy and toxicity of four standard antiepileptic drugs used as monotherapy in children with newly diagnosed epilepsy.
Between 1981 and 1987, 167 children aged 3-16 years, who had had at least two previously untreated tonic-clonic or partial seizures, with or without secondary generalisation, were randomly allocated treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform to standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to achieving 1-year remission.
The overall outcome with all four drugs was good. 20% of children remained free of seizures and 73% had achieved 1-year remission by 3 years of follow-up. We found no significant differences between the drugs for either measure of efficacy at 1, 2, or 3 years of follow-up. The overall frequency of unacceptable side-effects necessitating withdrawal of the randomised drug was 9%. This total included six of the first ten children assigned phenobarbitone; no further children were allocated this drug. Of the other three drugs, phenytoin (9%) was more likely to be withdrawn than carbamazepine (4%) or sodium valproate (4%). INTERPRETATION Our data will inform choice of drug and outcome with four of the standard drugs available for newly diagnosed tonic-clonic or partial seizures with or without secondary generalisation in children.
The Lancet 04/1996; 347(9003):709-13. · 39.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Remission of seizures is a crucial measure of outcome in epilepsy. The National General Practice Study of Epilepsy (NGPSE) aimed to investigate the remission of patients with epilepsy and the effect of various factors on the likelihood of remission. The NGPSE is a prospective population-based study free from major selection bias. We enrolled 1091 patients with newly diagnosed or suspected epilepsy who attended one of 275 general practices throughout the UK between 1984 and 1987. Remission was analysed in those patients who were classified after 6 months as having definite epilepsy (n = 564) or possible epilepsy (n = 228). After 9 years from the index seizure, 86% (95% CI 81-90) of patients with definite epilepsy had achieved a remission of 3 years and 68% (61-75) a remission of 5 years. For the complete cohort, including those with possible epilepsy, the remission rates at 9 years were 87% (83-91) for 3-year remission and 71% (65-77) for 5-year remission. The proportion of patients with definite epilepsy who were still in remission at 9 years' follow-up (terminal remission) was 68% (62-74) for 3-year and 54% (48-60) for 5-year remission. 61% (56-68) of patients with idiopathic seizures and 61% (46-75) of those with remote symptomatic epilepsy had achieved 5-year remission by 9 years. Overall, age and seizure type had little effect on the chances of achieving remission. This study confirms the good outcome for seizure control in the majority of patients.
The Lancet 08/1995; 346(8968):140-4. · 39.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent studies have shown that most newly diagnosed epileptic patients can be satisfactorily treated with a single antiepileptic drug. We therefore undertook a prospective randomised pragmatic trial of the comparative efficacy and toxicity of four major antiepileptic drugs, utilised as monotherapy in newly diagnosed epileptic patients. Between 1981 and 1987 243 adult patients aged 16 years or over, newly referred to two district general hospitals with a minimum of two previously untreated tonic-clonic or partial with or without secondary generalised seizures were randomly allocated to treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform with standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to enter one year remission. The overall outcome with all of the four drugs was good with 27% remaining seizure free and 75% entering one year of remission by three years of follow up. No significant differences between the four drugs were found for either measure of efficacy at one, two, or three years of follow up. The overall incidence of unacceptable side effects, necessitating withdrawal of the randomised drug, was 10%. For the individual drugs phenobarbitone (22%) was more likely to be withdrawn than phenytoin (3%), carbamazepine (11%), and sodium valproate (5%). In patients with newly diagnosed tonic-clonic or partial with or without secondary generalised seizures, the choice of drug will be more influenced by considerations of toxicity and costs.
[Show abstract][Hide abstract] ABSTRACT: 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.
The Lancet 11/1994; 344(8927):918-21. · 39.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A total of 276 patients with a high risk of developing postoperative seizures were randomised to treatment with carbamazepine or phenytoin for six or 24 months, or to no treatment. No significant differences were found (though the confidence limits were fairly wide) between the regimes in respect of the incidence of seizures or death. In a substantial proportion of the patients postoperative epilepsy remained a continuing disability. A high incidence of drug-related side effects was found in the treatment groups. Prophylactic anticonvulsants cannot therefore be recommended routinely following supratentorial craniotomy.
[Show abstract][Hide abstract] ABSTRACT: A prospective multicentre randomised study of continued antiepileptic treatment vs slow withdrawal was conducted in 1013 patients who had been free of seizures for at least 2 years. Comparison of randomised and eligible, but non-randomised, patients suggests the results should be applicable to a wider patient population. By 2 years after randomisation, 78% of patients in whom treatment was continued and 59% of those in whom it was withdrawn remained seizure free, but thereafter the differences between the two groups diminished. Non-compliance with continued treatment accounted for only a small proportion of the risk to the group continuing with treatment. The most important factors determining outcome were longer seizure-free periods (reducing the risk) and more than one antiepileptic drug and a history of tonic-clonic seizures (increasing the risk). Other factors (eg, history of neonatal seizures, specific electroencephalographic features) seemed to have smaller effects, but even in such a large study the confidence intervals for these observations were wide.
The Lancet 05/1991; 337(8751):1175–1180. · 39.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In newly diagnosed adult patients with epilepsy followed prospectively on monotherapy, carbamazepine and phenytoin were associated with a fall in plasma uric acid, but sodium valproate and phenobarbitone were associated with a rise in plasma uric acid. The mechanisms and significance of these findings are discussed.
Epilepsy Research 05/1991; 8(3):241-4. · 2.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the National General Practice Study of Epilepsy 564 patients classified as having definite seizures have been followed up for 2-4 years. 67% (95% confidence interval 63-71%) had a recurrence within 12 months of the first seizure, and 78% (74-81%) had a recurrence within 36 months. Seizures associated with a neurological deficit presumed present at birth had a high rate of recurrence (100% by 12 months), whereas seizures that occurred within 3 months of an acute insult to the brain, such as head injury or stroke, or in the context of an acute precipitant such as alcohol, carried a much lower risk of recurrence (40% [29-51%] by 12 months). Other factors affecting the risk of recurrence were age-the highest risk being for patients under the age of 16 (83% [77-89%] by 36 months) or over the age of 59 (83% [76-90%] by 36 months-and type of first seizure-the risk of recurrence being much higher for patients with simple partial or complex partial seizures (94% [90-99%] by 36 months) than for those with generalised tonic clonic seizures (72% [67-77%] by 36 months).
The Lancet 12/1990; 336(8726):1271-4. · 39.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The National General Practice Study of Epilepsy is a prospective population-based cohort study of 1195 patients with newly diagnosed or suspected epileptic seizures. At the time of initial classification (6 months after notification), 104 patients were excluded. Of the remaining 1091 patients, 220 (20% [95% confidence interval 18-23%]) had febrile seizures, 564 (52% [49-55%]) definite epileptic seizures, and 228 (21% [19-23%]) possible epilepsy. In the definite epilepsy group the proportions of males and females were similar, 25% (21-28%) were younger than 15 years and 24% (21-28%) were 60 years or older. The definite seizures were classified as cryptogenic in 62% (58-66%), remote symptomatic in 21% (18-25%), and acute symptomatic in 15% (12-18%). The aetiology of epilepsy was vascular disease in 15% (12-18%) and tumour in 6% (4-8%). Among older subjects the proportion with an identifiable cause was much higher: 49% (41-58%) were due to vascular disease and 11% (6-16%) to tumour. Only 252 (45% [41-49%]) of the 564 patients with definite epileptic seizures were registered at the time of their first seizure. 52% (48-56%) of the patients had partial or secondarily generalised seizures, and only 39% (35-43%) seizures generalised from the outset.
The Lancet 12/1990; 336(8726):1267-71. · 39.06 Impact Factor