Hydrocephalus and epilepsy

Since the introduction of ventriculo-atrial and/or ventriculo-peritoneal shunting for hydrocephalic patients, controversies have developed regarding the likelihood of epileptic seizures developing as a result of the shunting itself and/or its complications. On the other hand, hydrocephalus is not commonly recognized as a cause of seizures in general, although epilepsy is reported to be frequently associated with shunt-treated hydrocephalus, especially in children. Several authors have reported an increased risk of epileptic seizures after shunt placement, but the underlying mechanisms are still controversial. The insult to the brain at the time of ventricular catheter insertion, the presence of the shunt tube itself as a foreign body, the burr hole location, the number of shunt revisions after malfunction, associated infection, the etiology of hydrocephalus, and associated mental retardation are thought to be related to the risk of epilepsy. Age at the time of initial shunt placement also seems to be an important factor. Early shunting is a well-known determinant of risk in shunt obstruction, and children less than 2 years old are consequently at a higher risk of developing epilepsy than older ones. It is reported that antiepileptic drug treatment is not so reliable as might be expected. Conscientious and more sophisticated EEG recording in those children may be beneficial during follow-up. The incidence of seizures in shunted children is reported to be quite high, ranging from 20% to approximately 50%, so that neurosurgeons should pay more attention to the issue of epilepsy in hydrocephalic children. Although ventriculo- extracranial shunts have been the standard treatment for hydrocephalus for decades, the long-term morbidity, including postshunt epileptic seizures, has to be taken seriously. The use of neuroendoscopic techniques when indicated may ameliorate this problem a great deal in the future. Received: 1 June 2000     

Determinants of outcome in childhood epilepsy

Possible outcomes with regard to seizures include remission (i.e. no seizures without drug treatment), conditional remission (i.e. no seizures under treatment) and treatment resistance. Several factors have been identified which are associated with favourable or unfavourable outcomes. These include syndrome diagnosis (benign vs severe epilepsy syndromes), seizure types (kind and number), severity of epilepsy, response to treatment (immediate vs delayed, monotherapy vs combinations), and concomitant neurological and psychiatric disorders. However, the quality of disease management by caretakers also has an important influence on the outcome. To determine full remission in patients who are seizure-free with treatment, antiepileptic drugs need to be tapered; generally speaking, this seems to be less risky in children than in adults. However, even if remission without treatment has been reached, an elevated risk of seizures may persist compared with that of the general population. The outcome of epilepsy should not be considered with respect to seizures alone, but should also include more global aspects of performance and quality of life. These may depend on the causes of epilepsy as much as, or more than, on the seizure disorder itself, but may also be related to treatment.     

Prognosis of Epilepsy: A Review and Further Analysis of the First Nine Years of the British National General Practice Study of Epilepsy, a Prospective Population-Based Study

Summary: Purpose: To understand the prognosis of newly diagnosed epilepsy to provide rational therapy and advice for patients and their physicians. Methods: 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). Results: Only 33 patients were completely lost to follow-up. After 9 years, 86% [95% confidence interval (CI) 81, 901 of patients with definite epilepsy had achieved a remission of 3 years, and 68% (CI 61, 73, 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, 5.3, and for those with acute symptomatic epilepsy it was 2.9 (CI 1.7, 4.5). Conclusions: Overall, most patients with epilepsy wiil enter remission; however, there is a higher than expected risk of death, especially in those with symptomatic epilepsy.     

Outcomes After Seizure Recurrence in People with Well-Controlled Epilepsy and the Factors That Influence It

Summary: Purpose: To determine the risk of further seizures and probability of further remission after a first seizure recurrence in patients in remission of their epilepsy, and to examine the prognostic factors influencing this risk.
Methods: Continued follow-up of a cohort of 409 patients with a recurrence of seizures after randomization to the Medical Research Council (MRC) Antiepileptic Drug Withdrawal Study.
Results: By 3 years after a seizure, 95% of patients have experienced a further 1-year remission of their epilepsy and by 5 years 90% of patients have experienced a further 2-year remission. The most important factors contributing to the risk of further seizures after a first seizure after randomization were the previous seizure-free interval, having partial seizures at recurrence, and having previously experienced seizures while receiving treatment. There was no evidence that the group of patients who had discontinued or reduced treatment before the occurrence of their first seizure after randomization had a different outcome from those patients who continued treatment.
Conclusion: Our results provide no evidence that discontinuation of antiepileptic drugs (AEDs) modifies the long-term prognosis of a person's epilepsy, although it does increase the risk of seizures in the 1- to 2-year period after discontinuation.     

Epilepsy is a neurological and a systemic disorder

The basic pathophysiology of epilepsy is still not fully understood. Epidemiological evidence for epilepsy seems to suggest that it may not only be the propensity for seizures to occur. The high prevalence of comorbidity and the finding that premature mortality is still increased in those who are in long-term remission, suggest that there is a systemic component to the condition. This systemic component is an additional shared risk factor that can explain an important proportion of the comorbidities of epilepsy as well as how an individual with inactive epilepsy remains at an elevated risk of premature mortality. This systemic component can be viewed from the perspective of a number of fundamental pathophysiological processes: inflammation, oxidative stress, glycation, and methylation capacity. These processes are associated with all-cause mortality and there is also a growing understanding of their impact on seizure processes. We propose that epilepsy be considered as the sum of seizures and comorbidities caused by systemic dysfunction, and that the comprehensive management of epilepsy should also include the management of the systemic dysfunction.     

Predicting antiepileptic drug response in children with epilepsy

In clinical practice, after diagnosis and when treatment has begun, it is important to predict as soon as possible which children will become seizure-free and which are likely to develop medically intractable seizures. This article summarizes factors predicting seizure remission in childhood-onset epilepsy treated with antiepileptic drugs (AEDs). Sustained seizure remission can be expected in over 90% of idiopathic epilepsies of childhood and in neurologically normal children with epilepsy having infrequent seizures showing early remission after starting treatment with AEDs. Even in the presence of symptomatic etiology of epilepsy--focal seizures and syndromes; high seizure frequency prior to or during treatment; seizure clustering; and poor or delayed response to first adequate drug therapy--up to 60% of children with treated epilepsy are able to enter long-term remission. However, remission can be expected in only 30% or less of those with catastrophic epilepsies of childhood.     

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 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.     

Long-Term Prognosis in Childhood Epilepsy: Survival and Seizure Prognosis

All children aged 0-19 years who had active epilepsy in a defined Swedish population were traced and given a clinical and psychometric investigation. Twelve years later, a follow-up study was carried out. Eleven of the 194 children had died, 8 of whom had had signs of neurodeficit, i.e., abnormal neurology and/or mental retardation. A long-standing remission of seizures occurred in 124 of the 194 children. Signs of neurodeficit, frequent seizures, and many types of seizures were negative prognostic factors. The presence of all these factors carried a bad prognosis, seizures persisting during 12 years in greater than 80%. For those who were mentally and neurologically normal and had low seizure frequency, prognosis was excellent, only 11% still having active epilepsy after 12 years. A study of the annual remission rate showed that each year approximately 13% of the children without neurodeficit had remission from epilepsy the next year. This rate appeared to be stable over the 12 years studied. Among those children with neurodeficit, the annual remission rate was high only during the first years after onset, later falling to 3% a year.     

Refractory epilepsy in a Chinese population

OBJECTIVES: To investigate the proportion of Chinese patients with intractable seizures and the risk factors leading to refractory epilepsy. METHODS: Consecutive patients over 14 years of age attending a Neurology clinic were evaluated. Patients with epilepsy were classified into two groups according to their seizure control: refractory or seizure-free. Epilepsy was classified as idiopathic as defined by age-related onset and typical electroclinical characteristics, symptomatic if secondary to a structural abnormality and cryptogenic if the cause was unknown. Age, sex, epilepsy syndrome classification, aetiology, presence of mental retardation and the number of drugs used were compared between patients with refractory epilepsy and those in remission. RESULTS: Among 260 adolescent and adult patients with a mean age of 34 years (range 15-79), complete seizure control was achieved in 157 (60%) cases. Multivariate binomial logistic regression analysis showed that patients with mesial temporal sclerosis (OR=7.6, 95% CI 3.53-16.4, p<0.01) and the presence of mental retardation (OR=9.39, 95% CI 3.98-22.12, p<0.01) were more likely to develop pharmacoresistant epilepsy. CONCLUSION: In adults the underlying aetiology is an important factor as to whether patients develop intractable seizures. Poor control was also associated with the presence of mesial temporal sclerosis and mental retardation.     

Update on the epidemiology and prognosis of pediatric epilepsy

Epilepsy is among the most common serious neurologic disorders in childhood. Epidemiologic studies over the past few decades have greatly increased current knowledge of the incidence and prognosis of seizures. Newer epidemiologic studies have used population- or community-based cohorts, and careful attention has been given to etiology and specific epilepsy syndromes, the two most important factors affecting prognosis. Risk of epilepsy is highest in patients with an associated serious neurologic abnormality, such as mental retardation or cerebral palsy. More than two thirds of patients with childhood-onset epilepsy ultimately achieve remission. Of those attaining remission on medications, approximately 70% remain seizure free when medications are discontinued. Mortality is increased in patients with epilepsy, but the increased mortality risk in childhood-onset epilepsy is primarily seen in patients with neurologic abnormalities or intractable epilepsy. Although long-term seizure outcomes are generally favorable, childhood-onset epilepsy is associated with adverse long-term psychosocial outcomes, even in patients attaining remission. This review summarizes recent data on the epidemiology and prognosis of pediatric epilepsy.     

Seizures in patients with Alzheimer’s disease or vascular dementia: A population‐based nested case–control analysis

Purpose: Patients with Alzheimer’s disease (AD) have an increased risk of developing seizures or epilepsy. Little is known about the role of risk factors and about the risk of developing seizures/epilepsy in patients with vascular dementia (VD). The aim of this study was to assess incidence rates (IRs) of seizures/epilepsy in patients with AD, VD, or without dementia, and to identify potential risk factors of seizures or epilepsy. Methods: We conducted a follow‐up study with a nested case–control analysis using the United Kingdom–based General Practice Research Database (GPRD). We identified patients aged ≥65 years with an incident diagnosis of AD or VD between 1998 and 2008 and a matched comparison group of dementia‐free patients. Conditional logistic regression was used to estimate the odds ratio (OR) with a 95% confidence interval (CI) of developing seizures/epilepsy in patients with AD or VD, stratified by age at onset and duration of dementia as well as by use of antidementia drugs. Key Findings: Among 7,086 cases with AD, 4,438 with VD, and 11,524 matched dementia‐free patients, we identified 180 cases with an incident diagnosis of seizures/epilepsy. The IRs of epilepsy/seizures for patients with AD or VD were 5.6/1,000 person‐years (py) (95% CI 4.6–6.9) and 7.5/1,000 py (95% CI 5.7–9.7), respectively, and 0.8/1,000 py (95% CI 0.6–1.1) in the dementia‐free group. In the nested case–control analysis, patients with longer standing (≥3 years) AD had a slightly higher risk of developing seizures or epilepsy than those with a shorter disease duration, whereas in patients with VD the contrary was observed. Significance: Seizures or epilepsy were substantially more common in patients with AD and VD than in dementia‐free patients. The role of disease duration as a risk factor for seizures/epilepsy seems to differ between AD and VD.     

Familial Aggregation and Severity of Epilepsy

Genetic models for complex diseases frequently assume that genetic factors play a greater role in severe forms than in mild forms of disease. This study examined familial aggregation of epilepsy in relation to two measures of severity: duration and remission. The study population comprised 358 offspring born in Rochester, MN, U.S.A., to parents with epilepsy who were diagnosed in Rochester between 1935 and 1979 and followed for greater than or equal to 5 years after the first seizure. Cox proportional hazards analysis was used to examine the effects of duration of the parent's epilepsy (less than 5 vs. greater than or equal to 5 years) and remission of the parent's epilepsy (greater than or equal to 5 years seizure-free) on risk of unprovoked seizures in offspring. The univariate rate ratio (RR) for parent's duration (long vs. short) was 1.1 (95% confidence interval 0.32-3.57). The RR for parent's remission was 2.5 (0.55-11.41), reflecting a higher risk for offspring of remitting parents, which was not statistically significant. Multivariate analysis was used to control for three other parental attributes associated with offspring seizure risk: sex, age at onset of seizures (less than 20 vs. greater than or equal to 20 years), and seizure type (absence vs. other). The RR for duration was not substantially changed in this analysis (1.2; 0.37-4.16). However, the RR for remission dropped to 1.2 (0.25-5.97), suggesting that the higher risk in offspring of remitting parents was largely explained by confounding with other factors that influence offspring seizure risk.(ABSTRACT TRUNCATED AT 250 WORDS)     

Risk Factors for Sudden Unexpected Death in Epilepsy

Summary: The exact mechanisms of sudden unexpected death in individuals with epilepsy (SUDEP) are unclear, and only an incomplete analysis of risk factors can be made. Clinical, epidemiologic, and electrophysiologic evidence suggests that most sudden deaths are related temporally to seizures, are unwitnessed, and that many occur during sleep. Individuals with generalized seizures, symptomatic epilepsy, severe or frequent seizures, and additional mental handicap or neurologic deficit are at greater risk, and the majority of cases probably occur in patients with chronic epilepsy. Young people are more at risk for SUDEP than older people with epilepsy, and risk factors in pediatric practice may differ from those in adult epileptology.     

Cause-Specific Mortality in Epilepsy

Summary:  Epilepsy is associated with a two- to three-fold increase in mortality. Studies of cause-specific mortality show that deaths may be classified into those that are directly or indirectly related to epilepsy, those that are related to the underlying pathology giving rise to epilepsy, and those that are unrelated to both epilepsy and its causes. Overall, direct epilepsy related deaths are infrequent. Pneumonia, especially in the elderly, central nervous system (CNS) and non-CNS neoplasias, and cerebrovascular disease are frequent causes of death. Suicides, accidental deaths, and ischemic heart disease do not appear to be significant contributors to mortality in community-based studies. In hospital/institution-based analyses, epilepsy-related deaths are common and sudden unexpected death in epilepsy (SUDEP) may account for up to 17% of all deaths in epilepsy. A small proportion of these deaths may be witnessed and most such witnessed deaths occur in relation to convulsive seizures. The exact pathogenetic mechanisms are unknown although it is very probable that lack of seizure control is an important risk factor. Patients who continue to suffer seizures appear to have an almost 40 times higher risk of mortality than those in remission.     

Diagnosing and predicting refractory epilepsy

Over 30% of people with epilepsy will never achieve remission with antiepileptic drug (AED) therapy. These individuals are often severely disabled by their condition, have an unsatisfactory quality of life, and are at increased risk of sudden unexpected death. Early identification of refractory epilepsy would allow prompt referral to specialist services, where the diagnosis can be confirmed, seizures and syndromes classified, AED therapy optimized, and suitability for surgery assessed. Recent studies suggest that patients with symptomatic or cryptogenic epilepsy, those who experience multiple seizures before AED treatment initiation, and those with febrile convulsions, a family history of epilepsy, or psychiatric comorbidities are least likely to respond to drug therapy. Failure to achieve good seizure control with the first one or two AED monotherapies is usually sufficient to highlight the possibility of subsequent refractory epilepsy. For most of these individuals, combination therapy using AEDs with complementary modes of action is the recommended treatment approach.     

Remission of Seizures and Relapse in Patients with Epilepsy

In a longitudinal study of patients with epilepsy in Rochester, Minnesota, we found that the probability of being in remission (at least 5 consecutive years seizure-free, and continuing) at 20 years after diagnosis was 70%. The rates for remission we encountered were generally higher than those previously reported. We believe that the better prognosis in our series results from inclusion of all incidence cases in a defined population, beginning at the initial diagnosis of epilepsy. Prognosis for remission of epilepsy is poor in patients with associated neurologic dysfunction identified from birth. Patients with idiopathic seizures and survivors of postnatally acquired epilepsy have better prospects for eventual remission. The probability of remission is highest in patients with generalized-onset seizures diagnosed before 10 years of age. Prognosis is less favorable for those with partial complex seizures and adult-onset epilepsy.     

Clinical predictors of late-onset seizures and epilepsy in patients with cerebrovascular disease

BACKGROUND: Seizures and epilepsy are harmful and worsen the disability of stroke patients. There are currently no good clinical predictors of late-onset seizures and epilepsy in patients with cerebrovascular disease (CVD). PATIENTS AND METHODS: 110 patients with delayed seizures after an ischaemic or a haemorrhagic stroke, a transient ischaemic attack or a subarachnoid haemorrhage (60 with a single seizure and 50 with epilepsy) and 366 without seizures were included in this retrospective study. The clinical syndrome, the stroke aetiology and the vascular risk factors were compared. The groups with a single seizure and with epilepsy were also analysed separately. RESULTS: There were no differences in age, gender, aetiology and vascular risk factors between the groups with and without seizures. When comparing the incidence of the clinical syndromes, ischaemic partial anterior circulation syndrome (PACS) was significantly more and transient ischaemic attack less frequent in the group with seizures compared to the control group. The severity of the neurological impairment on admission and the degree of disability on discharge after a PACS was similar in those who developed late-onset seizures compared with those who did not. Also on the Cox proportional hazards analysis, PACS appeared to be the only clinical risk factor for development of seizures and epilepsy in patients with CVD. No differences were observed in clinical predictors between patients with a single seizure and those with epilepsy. CONCLUSION: PACS is the only independent predictor for the occurrence of late-onset seizures in patients with CVD.     

Epilepsy in hemiplegic cerebral palsy due to perinatal arterial ischaemic stroke

Aim The aim of this study was to describe the frequency, risk factors, manifestations, and outcome of epilepsy in children with hemiplegic cerebral palsy (CP) due to perinatal arterial ischaemic stroke (AIS). Method The study group comprised 63 participants (41 males, 22 females) from a population‐based CP register whose brain imaging showed perinatal AIS. Information collected included occurrence of neonatal seizures, family history of epilepsy, motor function and epilepsy onset, treatment, and outcome. Electroclinical findings were classified according to seizure semiology, seizure type, and epilepsy syndrome. Results Mean age of participants at the time of study was 10 years 6 months (SD 4y 7mo, range 4–20y). Gross Motor Function Classification System levels I and II were reported in 96% of participants, and Manual Ability Classification System levels I and II were reported in 79% of children. Thirty‐four children (54%) developed epilepsy. Term delivery and more severe motor impairment were associated with epilepsy, but neonatal seizures and family history of epilepsy were not. Initial seizures were epileptic spasms, focal seizures, or myoclonic seizures. Focal seizure semiology suggested Rolandic or occipital seizure origin in the majority of children. Focal epileptic discharges in children with focal seizures had features of idiopathic partial epilepsy. Only 15% of children had active epilepsy 10 years after onset. Interpretation Despite a high incidence of epilepsy in children with hemiplegic CP due to AIS, the prognosis for seizure remission is good. Many children have clinical features, electroencephalography findings, and remission typical of idiopathic partial epilepsy.     

The prognosis of epilepsy.

The cardinal question for a person developing seizures is ‘What is the likelihood that they will go away?’ ‘Prognosis’ refers to the possible outcomes of a disease and the frequency at which they can be expected to occur. Prognostic factors may include demographic features, disease-specific indicators (e.g. seizure frequency, aetiology of epilepsy) or co-morbidity. Such factors do not necessarily cause the outcome, but they are associated strongly with the outcome measured. They are distinct from risk factors—which are associated with the initial development of the disorder. Ideas about the outcome for epilepsy have been altered radically in the past century by study of its epidemiology. The prognosis for epilepsy comprises a number of measurable end-points: the prediction of recurrence after a single unprovoked seizure, the chance of remission after the diagnosis of epilepsy and the risk of premature death.     

Prevalence of epilepsy—An unknown quantity

The incidence, prevalence, and mortality of epilepsy vary across countries with different economies. Differences can be explained by methodological problems, premature mortality, seizure remission, socioeconomic factors, and stigma. Diagnostic misclassification—one possible explanation—may result from inclusion of patients with acute symptomatic or isolated unprovoked seizures. Other sources of bias include age and ethnic origin of the target population, definitions of epilepsy, retrospective versus prospective ascertainment, sources of cases, and experienced and perceived stigma. Premature mortality is an issue in low‐income countries (LICs), where treatment gap, brain infections, and traumatic brain injuries are more common than in high‐income countries (HICs). Death rates may reflect untreated continued seizures or inclusion of acute symptomatic seizures. Lack of compliance with antiepileptic drugs has been associated with increased risk for death, increased hospital admissions, motor vehicle accidents, and fractures in poor communities. Epilepsy is a self‐remitting clinical condition in up to 50% of cases. Studies in untreated individuals from LICs have shown that the proportion of remissions overlaps that of countries where patients receive treatment. When the identification of patients is based on spontaneous reports (e.g., door‐to‐door surveys), patients in remission may be less likely to disclose the disease for fear of stigmatization with no concurrent benefits. This might lead to underascertainment of cases when assessing the lifetime prevalence of epilepsy. In LICs, the proportion of people living in poverty is greater than in HICs. Poverty is associated with risk factors for epilepsy, risk for developing epilepsy, and increased mortality. The high incidence and prevalence of epilepsy found in LICs is also observed in low income individuals from HICs. Epileptogenic conditions are associated with an increased mortality. This may partly explain the difference between incidence and lifetime prevalence of epilepsy in LICs. Poverty within LICs and HICs could be a preventable cause of mortality in epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .