Matti Sillanpää

Long-Term Prognosis of Seizures with Onset in Childhood

BACKGROUND The long-term prognosis of seizures that begin in childhood is uncertain. METHODS We prospectively studied 245 children from the catchment area of Turku University Hospital in Turku, Finland, who had active epilepsy diagnosed between 1961 and 1964. Sixty-eight patients (28 percent) had idiopathic seizures (presumed to have a genetic origin), 54 (22 percent) had cryptogenic seizures (occurring in otherwise normal persons with no clear cause), and 123 (50 percent) had remote symptomatic seizures (with no immediate cause but occurring in persons with a prior brain injury or a static encephalopathy). RESULTS At the final follow-up in 1992, we had sufficient data on 220 patients (90 percent), 176 of whom were alive and 44 of whom had died; the remaining 25 had emigrated, could not be traced, or declined to participate. Thirty-nine patients who died were not free of seizures at the time of death, and 33 had remote symptomatic seizures. Among the surviving patients, 112 (64 percent) had been seizure-free for at least five years, including 83 (47 percent) who were not taking antiepileptic medications. The most important predictors of being seizure-free for at least five years were a rapid response to therapy (defined as a reduction in the frequency of seizures of 75 to 100 percent within three months of beginning treatment) and a diagnosis of idiopathic seizures. As compared with a matched control group, 99 patients with epilepsy but no other initial neurologic impairment were of similar socioeconomic status and had similar rates of passing an examination given after 12 years of school. Significantly more patients, however, had completed only six years of school (relative risk, 2.13), were unemployed (relative risk, 3.76), were not married (relative risk, 3.50), and did not have children (relative risk, 3.00). CONCLUSIONS Although the majority of patients with epilepsy in childhood are free of seizures by the time they become adults, they are at increased risk for social and educational problems. Patients whose epilepsy does not remit also have an increased risk of death.

Sudden unexpected death in epilepsy: a review of incidence and risk factors.

Summary:  Sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy‐related cause of death. However, SUDEP is rare in patients with new onset epilepsy and in patients in remission. Incidence is about 0.35 cases/1,000 person‐years in population‐based incidence cohort of epilepsy. Incidence is considerably higher in patients with chronic epilepsy, 1–2/1,000 person‐years, and highest with severe, refractory seizures, 3–9/1,000. The highest rates occur from 20 to 40 years. Most SUDEP appears seizure‐related. When witnessed, the fatal event generally occurred in association with generalized tonic–clonic seizure. Two recent case–control studies suggest that seizure frequency is the strongest risk factor for SUDEP: relative risk = 23 (95% CI = 3.2–170) for persons with ≥1 seizure during the year of observation versus seizure‐free patients. Onset of epilepsy at an early age and long duration of the disorder are other risk factors. Although SUDEP has not been associated with the use of any particular antiepileptic drugs (AEDs), some case–control studies have pointed to an association between SUDEP and polytherapy with AEDs and frequent dose changes independent of seizure frequency. Although recent epidemiological studies have been helpful in identifying patients at risk for SUDEP, providing clues to mechanisms behind SUDEP, no single risk factor is common to all SUDEP, suggesting multiple mechanisms or trigger factors. Seizure control seems of paramount importance to prevent SUDEP. Further large‐scale case–control studies are needed to assess the role of AEDs in order to form a basis for treatment strategies aiming at seizure control and prevention of SUDEP.

Long-term mortality in childhood-onset epilepsy.

BACKGROUND There are few studies on long-term mortality in prospectively followed, well-characterized cohorts of children with epilepsy. We report on long-term mortality in a Finnish cohort of subjects with a diagnosis of epilepsy in childhood. METHODS We assessed seizure outcomes and mortality in a population-based cohort of 245 children with a diagnosis of epilepsy in 1964; this cohort was prospectively followed for 40 years. Rates of sudden, unexplained death were estimated. The very high autopsy rate in the cohort allowed for a specific diagnosis in almost all subjects. RESULTS Sixty subjects died (24%); this rate is three times as high as the expected age- and sex-adjusted mortality in the general population. The subjects who died included 51 of 107 subjects (48%) who were not in 5-year terminal remission (i.e., ≥5 years seizure-free at the time of death or last follow-up). A remote symptomatic cause of epilepsy (i.e., a major neurologic impairment or insult) was also associated with an increased risk of death as compared with an idiopathic or cryptogenic cause (37% vs. 12%, P<0.001). Of the 60 deaths, 33 (55%) were related to epilepsy, including sudden, unexplained death in 18 subjects (30%), definite or probable seizure in 9 (15%), and accidental drowning in 6 (10%). The deaths that were not related to epilepsy occurred primarily in subjects with remote symptomatic epilepsy. The cumulative risk of sudden, unexplained death was 7% at 40 years overall and 12% in an analysis that was limited to subjects who were not in long-term remission and not receiving medication. Among subjects with idiopathic or cryptogenic epilepsy, there were no sudden, unexplained deaths in subjects younger than 14 years of age. CONCLUSIONS Childhood-onset epilepsy was associated with a substantial risk of epilepsy-related death, including sudden, unexplained death. The risk was especially high among children who were not in remission. (Funded by the Finnish Epilepsy Research Foundation.).

Increasing Prevalence of Headache in 7‐Year‐Old Schoolchildren

Reports of increased prevalence of headache in adults end clinical impressions of similar trends in children prompted this epidemiological study on migraine and other headache. The first stage was carried out in 1974 In children starting school, and the second stage in 1992 using the identical study design, the same age group, and a similar urban child population.

Mortality of Epilepsy in Developed Countries: A Review

Summary:  Mortality in people with epilepsy has been studied in many different populations. In population‐based incidence cohorts of epilepsy with 7–29 years follow‐up, there was up to a threefold increase in mortality, compared to the general population (standardized mortality ratios [SMR] ranged from 1.6 to 3.0). When studies include selected epilepsy populations where patients with frequent and severe seizures are more common, the mortality is even greater. Relative survivorship (RS) following the diagnosis of epilepsy was 91%, 85%, and 83% after 5, 10, and 15 years, respectively. In a population with childhood‐onset epilepsy, RS was 94% and 88% after 10 and 20 years.

Remission of Seizures and Predictors of Intractability in Long‐Term Follow‐Up

In an incidence cohort, remission and relapse rates and determinants were studied in 178 patients followed long‐term. A comparative study of predictive factors was performed in 40 patients with histories of antiepileptic (AED)‐drug‐refractory epileptic seizures in the last 10 years of follow‐up and compared with the other 138 cohort subjects. The two groups were cross‐tabulated with 353 variables of family history, obstetric, developmental and seizure histories, and current medical and social status. Multivariate analyses were applied for control of confounding. Defined or probable remote symptomatic etiology of seizures, abnormal neurologic development/ status, high initial seizure frequency, occurrence of status epilepticus, and poor short‐term effects of AED therapy were significantly associated with long‐term AED refractoriness. On logistic regression analyses, poor short‐term outcome of AED therapy [odds ratio (OR) 3.6; 95% confidence interval (CI) 1.2–10.4], occurrence of status epilepticus (OR 11.4; 95% CI 3.2–41.0), high initial seizure frequency (OR 4.6; 95% CI 1.1–19.3), and remote symptomatic seizure etiology (OR 2.9; 95% CI 1.1–8.2) remained the only independent predictors of seizure intractability. These factors enable early assessment of need for epilepsy surgery.

Social Adjustment and Competence 35 Years After Onset of Childhood Epilepsy: A Prospective Controlled Study

Summary: Purpose: To study the effect of childhood‐onset epilepsy without other neurologic deficit on adult social adjustment and competence.

Epilepsy in Children: Prevalence, Disability, and Handicap

Summary: Little is known about the handicapping effect of epilepsy without other neurological deficits on an epileptic individuals life. The purpose of this study was to collect information on the occurrence of disabilities and handicaps in an unselected population sample of children, 4–15 years of age, and to compare the results with matched controls. The prevalence of epilepsy in the study population was 0.68% (143/21,104). Time elapsed from last seizure was at least 1 year in 62.1% of the cases. There was marked neurologic comorbidity in the children with epilepsy; an accessory neurological deficit was found in 39.9%, the most frequent neurological impairments being mental retardation (31.4%), speech disorders (27.5%), and specific learning disorders (23.1%). A handicap was experienced in 20.7% of children with epilepsy only; i.e., with no other neurologic impairments, compared to 0.9% of matched controls. This means a 21.7‐fold (95% CI, 6.3–74.5) risk of the occurrence of a handicap in children with epilepsy compared to controls. Orientation and social integration handicaps were significantly more frequent in children with epilepsy only compared to controls. Occurrence of communication disability, situational disability, or satisfactory to poor economic status of the family were the independent predictors of the occurrence of a handicap in children with epilepsy only.

Perceived Impact of Childhood‐onset Epilepsy on Quality of Life as an Adult

Summary:  Purpose: Childhood‐onset epilepsy is a common disorder. The long‐term impact of having childhood epilepsy on quality of life (QOL) as an adult, whether or not seizures are in remission, has not been systematically studied.

Prevalence of headache at preschool age in an unselected child population

In a representative study of 5356 five-year-old children, 4405 (82.2%) could be traced for follow-up. Headache occurred in 861 (19.5%) of them; highly frequently in 0.2%, fairly frequently in 0.5%, less frequently in 4.3% and infrequently in 14.5%. Type of dwelling was the only predictor of housing standard, the risk of headache being about 1.5–fold in children living in other than one-family houses. Low economic status of the family, nursery day care and an increasing number of leisure activities were additional risk factors. Compared with infrequent or no headache, those with highly frequent or fairly frequent headache were at a 1.4–fold risk of temper tantrums. The risk of stomach ache was 8.9–fold in children with infrequent headache and 13.7–fold in those with fairly frequent or frequent headache compared with children with no headache.