Differences in brain changes between adults with childhood-onset epilepsy and controls: A prospective population-based study.

PURPOSE: To determine the impact of childhood-onset uncomplicated epilepsy (COE) on brain aging over 50-year prospective follow-up. METHODS: A population-based cohort of 41 aging subjects with COE and their 46 matched controls participated in a detailed in-person prospective assessment in 2012 and 2017 to characterize ongoing changes in the aging brain. RESULTS: The mean age of the COE participants was 63.2 years (SD 4.14, median 63.2, range 55.8-70.6) and 63.0 years (mean, SD 4.13, median 63.3, range 56.0-69.9) years for controls. Neurologic signs were significantly more common in COE participants not in remission (p = .015), and the most frequent abnormalities were cerebellar signs (p < .001). Neurologic signs in general (p = .008) and cerebellar signs in particular (p = .018) were significantly more common in focal than in generalized epilepsies. MRI white matter abnormalities were significantly associated with absence of vocational education (p = .011), and MRI hippocampal atrophy in COE subjects was associated with arterial hypertension versus normal blood pressure (p = .017). In the combined study cohort of COE subjects and controls, presenting neurologic signs increased both in the subjects and in the controls from the 2012 to 2017 study. CONCLUSIONS: At ultra-long-term follow-up, clinical and neuroimaging findings show tendencies to brain aging that is more accelerated in COE participants with active adult childhood-onset epilepsy, and particularly in focal epilepsy.

Parental distress rating at the child's age of 15 years predicts probable mental diagnosis: a three-year follow-up.

BACKGROUND: Mental health in adolescence is an increasing global public health concern. Over half of all mental disorders debut by 14 years of age and remain largely untreated up to adulthood, underlining the significance of early detection. The study aimed to investigate whether parental distress rating at the child's age of 15 predicts a probable mental diagnosis in a three-year follow-up. METHODS: All data was derived from the Finnish Family Competence (FFC) Study. The analysis focused on whether parental CBCL (Child Behavior Checklist) rating (n = 441) at the child's age of 15 years predicted the outcome of the child's standardised DAWBA (Development and Well-Being Assessment) interview at offspring's 18 years. RESULTS: Multivariable analysis showed that a one-unit increase in the total CBCL scores increased the relative risk of a DAWBA-based diagnosis by 3% (RR [95% CI] 1.03 [1.02-1.04], p < 0.001). CONCLUSIONS: Parental CBCL rating in a community sample at the adolescent's age of 15 contributes to early identification of adolescents potentially at risk and thus benefitting from early interventions.

Neurocognition in childhood epilepsy: Impact on mortality and complete seizure remission 50 years later.

OBJECTIVE: To study associations of the severity of impairment in childhood neurocognition (NC) with long-term mortality and complete seizure remission. METHODS: A population-based cohort of 245 subjects with childhood onset epilepsy was followed up for 50 years (median = 45, range = 2-50). Childhood NC before age 18 years was assessed as a combination of formal intelligence quotient scores and functional criteria (school achievement, working history, and psychoneurological development). Impaired NC was categorized with respect to definitions of intellectual functioning in International Classification of Diseases, 10th revision (R41.83, F70-F73). The outcome variables, defined as all-cause mortality and 10-year terminal remission with the 5 past years off medication (10YTR), were analyzed with Cox regression models. RESULTS: Of the 245 subjects, 119 (49%) had normal childhood NC, whereas 126 (51%) had various degrees of neurocognitive impairment. During the 50-year observation period, 71 (29%) of the subjects died, 13% of those with normal and 44% of those with impaired NC. The hazard of death increased gradually in line with more impaired cognition, reaching significance in moderate, severe, and profound impairment versus normal NC (hazard ratio [Bonferroni corrected 95% confidence interval] = 3.3 [1.2-9.2], 4.2 [1.2-14.2], and 5.5 [2.4-12.3], respectively). The chance for 10YTR was highest among subjects with normal NC (61%), whereas none of those with profound impairment reached 10YTR. In the intermediate categories, the chance was, however, not directly related to the increasing severity of impairment. SIGNIFICANCE: The severity of neurocognitive impairment during childhood shows a parallel increase in the risk of death. In comparison with normal NC, subjects with lower childhood NC are less likely to enter seizure remission. However, normal NC does not guarantee complete remission or prevent premature death in some individuals with childhood onset epilepsy.

Overrepresentation of epilepsy in children with type 1 diabetes is declining in a longitudinal population study in Finland.

AIM: The aim was to determine temporal changes in increased risk of epilepsy among children with type 1 diabetes. METHODS: The incidence of epilepsy up to age 15 in children with prior type 1 diabetes was analysed regarding the general Finnish child population using data from the Finnish nationwide hospital register. Type 1 diabetes and epilepsy were identified by the International Classification of Diseases 9th and 10th revision codes. Epilepsy was defined according to ILAE guidelines. The analyses were done using negative binomial regression models. RESULTS: Preceding type 1 diabetes was diagnosed in 6162 (0.91%) of the 679 375 general children population. Incidence rate of new-onset epilepsy among children with type 1 diabetes was higher than in controls (140 vs 82 per 100 000 person-years at risk, respectively). The excess incidence diminished with time (P = 0.033 for diabetes to birth cohort interaction), from over twofold in birth cohort 1990-1993 [incidence rate ratio 2.2 (95% CI 1.7-2.9)] to 40% in birth cohort 1998-2000 [1.4 (95% CI 1.001-1.9)]. CONCLUSION: In a population study setting, children with type 1 diabetes had an increased, but slowly declining risk of developing epilepsy. Future research may elucidate the underlying mechanisms.

Adolescent with caries and experienced interaction with dental staff.

BACKGROUND: There is a lack of studies about how adolescents experience the interaction during dental visits. The experienced interaction during dental visits will influence how adolescents take care of their oro-dental health, and how they attend at the dentist's office. AIM: To explore the interaction experiences during dental visits of 18-year-olds with or without a history of caries. DESIGN: The dental health status at age 15 years was used as a predictor of subsequent interaction experiences with the dental staff. The dental health status was assessed by the Decayed Missed Filled Teeth index and interaction experiences by the Patient Dental Staff Interaction Questionnaire. RESULTS: Adolescents with a history of caries experienced the interaction at dental visits significantly more often negatively than adolescents with healthy teeth. The association was significant after adjustment for potential confounding factors (sense of coherence, gender, and duration of maternal basic education). CONCLUSIONS: Understanding, encouraging, and appropriate interaction with adolescents with caries may make patients more positive and receptive for treatment and self-care.

Commonalities in epileptogenic processes from different acute brain insults: Do they translate?

The most common forms of acquired epilepsies arise following acute brain insults such as traumatic brain injury, stroke, or central nervous system infections. Treatment is effective for only 60%-70% of patients and remains symptomatic despite decades of effort to develop epilepsy prevention therapies. Recent preclinical efforts are focused on likely primary drivers of epileptogenesis, namely inflammation, neuron loss, plasticity, and circuit reorganization. This review suggests a path to identify neuronal and molecular targets for clinical testing of specific hypotheses about epileptogenesis and its prevention or modification. Acquired human epilepsies with different etiologies share some features with animal models. We identify these commonalities and discuss their relevance to the development of successful epilepsy prevention or disease modification strategies. Risk factors for developing epilepsy that appear common to multiple acute injury etiologies include intracranial bleeding, disruption of the blood-brain barrier, more severe injury, and early seizures within 1 week of injury. In diverse human epilepsies and animal models, seizures appear to propagate within a limbic or thalamocortical/corticocortical network. Common histopathologic features of epilepsy of diverse and mostly focal origin are microglial activation and astrogliosis, heterotopic neurons in the white matter, loss of neurons, and the presence of inflammatory cellular infiltrates. Astrocytes exhibit smaller K+ conductances and lose gap junction coupling in many animal models as well as in sclerotic hippocampi from temporal lobe epilepsy patients. There is increasing evidence that epilepsy can be prevented or aborted in preclinical animal models of acquired epilepsy by interfering with processes that appear common to multiple acute injury etiologies, for example, in post-status epilepticus models of focal epilepsy by transient treatment with a trkB/PLCγ1 inhibitor, isoflurane, or HMGB1 antibodies and by topical administration of adenosine, in the cortical fluid percussion injury model by focal cooling, and in the albumin posttraumatic epilepsy model by losartan. Preclinical studies further highlight the roles of mTOR1 pathways, JAK-STAT3, IL-1R/TLR4 signaling, and other inflammatory pathways in the genesis or modulation of epilepsy after brain injury. The wealth of commonalities, diversity of molecular targets identified preclinically, and likely multidimensional nature of epileptogenesis argue for a combinatorial strategy in prevention therapy. Going forward, the identification of impending epilepsy biomarkers to allow better patient selection, together with better alignment with multisite preclinical trials in animal models, should guide the clinical testing of new hypotheses for epileptogenesis and its prevention.

Long term outcome of childhood onset headache: A prospective community study.

Purpose To examine prevalence, course, and long-term outcome of childhood migraine and other headaches. Method Using questionnaires, 1185 children were followed for recurrent headaches at ages seven, 14 and 32 years, respectively. Results At age seven years, 4.0% of the 1185 children (girls 3.7%, boys 4.3%) had migraine and 24% (25%/23%) had nonmigrainous headache. In adulthood, 16% (22%/8%) had migraine and 60% (64%/54%) nonmigrainous headache. Childhood migraine persisted into adulthood in 65% of females and 21% of males, and nonmigrainous headache in 62% and 59%, respectively. After childhood, 17% of females and 7% of males started to have episodes of migraine. No recurrent headache during the follow-up was reported by 11% (6%/16%). In a multivariate analysis, compared with no childhood headache, childhood migraine increased the risk of adulthood migraine by 3.36-fold (95% CI 1.94-5.82) and that of nonmigrainous headache by 1.72-fold (1.14-2.60). Discussion and conclusions Headaches are generally as common in preschool girls as boys. From early school years, headaches steadily increase up to young adulthood, but among boys the prevalence levels off after adolescence. About two thirds of children experienced changes in their headache status during a 25-year follow-up. Any kind of recurrent headache at school entry predicts an increased risk of headache in young adulthood. Special attention should be paid to girls and particularly those girls who have recurrent headache when they start school.

Brain structure and organization five decades after childhood onset epilepsy.

The purpose of this project was to characterize brain structure and organization in persons with active and remitted childhood onset epilepsy 50 years after diagnosis compared with healthy controls. Participants from a population-based investigation of uncomplicated childhood onset epilepsy were followed up 5 decades later. Forty-one participants had a history of childhood onset epilepsy (mean age of onset = 5.2 years, current chronological age = 56.0 years) and were compared with 48 population-based controls (mean age = 55.9 years). Of the epilepsy participants, 8 had persisting active epilepsy and in 33 the epilepsy had remitted. All participants underwent 3T MRI with subsequent vertex analysis of cortical volume, thickness, surface area and gyral complexity. In addition, cortical and subcortical volumes, including regions of the frontal, parietal, temporal, and occipital lobes, and subcortical structures including amygdala, thalamus, and hippocampus, were analyzed using graph theory techniques. There were modest group differences in traditional vertex-based analyses of cortical volume, thickness, surface area and gyral index, as well as across volumes of subcortical structures, after correction for multiple comparisons. Graph theory analyses revealed suboptimal topological structural organization with enhanced network segregation and reduced global integration in the epilepsy participants compared with controls, these patterns significantly more extreme in the active epilepsy group. Furthermore, both groups with epilepsy presented a greater number of higher Z-score regions in betweenness centrality (BC) than lower Z-score regions compared with controls. Also, contrary to the group with remitted epilepsy, patients with active epilepsy presented most of their high BC Z-score regions in subcortical areas including the amygdala, thalamus, hippocampus, pallidum, and accumbens. Overall, this population-based investigation of long term outcome (5 decades) of childhood onset epilepsy reveals persisting abnormalities, especially when examined by graph theoretical measurements, and provides new insights into the very long-term outcomes of active and remitted epilepsy. Hum Brain Mapp 38:3289-3299, 2017. © 2017 Wiley Periodicals, Inc.

Remission in epilepsy: How long is enough?

OBJECTIVE: The International League Against Epilepsy (ILAE) has proposed to expand the definition of remission to 10 years seizure-free with the last 5 years off antiepileptic drugs (AEDs). We examined if a 10-year remission is needed to predict the lowest recurrence risk. METHODS: The population-based study cohort consisted of 148 patients with new-onset childhood epilepsy living in the catchment area of Turku University Hospital. They were prospectively followed for 44 years (median). Patients in first remission were prospectively followed for the duration of remission or possible relapse at 2 years in remission with the last year without antiepileptic drugs (AEDs), at 5 years in remission with the last 2 years without AEDs, and at 10 years with the last 5 years without AEDs. For comparison of the proportions of relapsed patients within each remission category exact Clopper Pearson 95% confidence intervals were used. RESULTS: The magnitude of the relapse rate estimates off AEDs did not significantly improve when remission increased from 2 years (2YR) to 5 years (5YR) and further to 10 years (10YR). However, 10YR was a more sensitive measure of no relapse than 2YR. Among patients with remission on or off AEDs, the ability to predict lower relapse rate increased markedly from 2 to 5 years, and again from 5 to 10 years. The risk of relapse was virtually the same estimated after 2YR off AEDs as after 10YR on or off AEDs, except for patients with generalized epilepsy whose 2YR off AEDs was a weaker predictor than 10YR on or off AEDs. SIGNIFICANCE: Given the modest differences in relapse rates between the 5 years seizure-free with last 2 years off medications definition and the 10 years seizure-free with last 5 years off medications, and the adverse impact of not being considered in remission, we propose that a return to the 5-year definition may be warranted.

Cognitive Outcome in Childhood-Onset Epilepsy: A Five-Decade Prospective Cohort Study.

OBJECTIVES: Little is known about the very long-term cognitive outcome in patients with childhood-onset epilepsy. The aim of this unique prospective population-based cohort study was to examine cognitive outcomes in aging participants with childhood-onset epilepsy (mean onset age=5.3 years) five decades later (mean age at follow-up=56.5 years). METHODS: The sample consisted of 48 participants with childhood-onset epilepsy and 48 age-matched healthy controls aged 48-63 years. Thirty-six epilepsy participants were in remission and 12 continued to have seizures. Cognitive function was examined with 11 neuropsychological tests measuring language and semantic function, episodic memory, and learning, visuomotor function, executive function, and working memory. RESULTS: The risk of cognitive impairment was very high in participants with continuing seizures; odds ratio (OR)=11.7 (95% confidence interval [CI] (2.8, 49.6), p=.0008). They exhibited worse performances across measures of language and semantic function, and visuomotor function compared to participants with remitted epilepsy and healthy controls. In the participants with remitted epilepsy, the risk of cognitive impairment was somewhat elevated, but not statistically significant; OR=2.6 (95% CI [0.9, 7.5], p=.08). CONCLUSIONS: Our results showed that the distinction of continued versus discontinued seizures was critical for determining long-term cognitive outcome in childhood-onset epilepsy. Few participants in remission exhibited marked cognitive impairment compared to age-matched peers. However, a subgroup of participants with decades long active epilepsy, continuous seizure activity and anti-epileptic drug (AED) medication, showed clinically significant cognitive impairment and are thus in a more precarious position when entering older age. (JINS, 2017, 23, 332-340).

Prevention of Epilepsy: Issues and Innovations.

Epilepsy is a common brain disease and preventing epilepsy is a very relevant public health concern and an urgent unmet need. Although 40 % of all epilepsy cases are thought to have acquired causes, there is a roadblock for successful prevention. Efforts to protect the brain from epileptogenic insults are severely hampered by our lack of biomarkers to identify the few percent at high risk meriting treatment among those exposed. Preventing brain injury has been moderately effective from around birth to middle age; however, the strategy has failed to stop a substantial increase over the last decades in symptomatic epilepsy in those aged 65 and above. The traditional concept of repurposing anti-seizure drugs used for symptomatic seizure relief to prevent the onset of epilepsy has completely failed up to now. More recently, however, hope is on the horizon with a search for biomarkers and discovery of a new class of agents, called anti-epileptogenic drugs, which were specifically developed for prevention of epilepsy.

Long-term changes in the incidence of childhood epilepsy. A population study from Finland.

BACKGROUND: The incidence of childhood epilepsy has changed during the past decades, but it is unclear whether it increased or decreased. METHODS: Changes in drug-treated childhood epilepsy between 1968 and 2012 were evaluated using the Finnish nationwide register of all children, aged ≤15years, on antiepileptic drugs (AEDs) prescribed for the treatment of epilepsy. The first registered entitlement to full-refundable AEDs was used as a proxy for newly diagnosed epilepsy. Incidence densities were calculated as ratios of annual new cases per 100,000person-years in each calendar year during 1968 to 2012. RESULTS: The annual incidence density of newly treated childhood epilepsy increased from 35 in the 1960s to 87 per 100,000person-years in the 1990s and decreased thereafter to 61 per 100,000person-years. Since 1996, the incidence density decreased 1-2% per year in children aged <1, 1-5, or 6-10years (all 95% confidence intervals within 0.3%-3%), while no substantial change was seen in older children. CONCLUSION: The incidence of drug-treated childhood epilepsy from the late 1960s to the early 1990s distinctly increased. The reasons for the increase are not fully understood but may include increasing ascertainment through improved diagnosis and a wider acceptance of AED treatment. Since the 1990s, a slight decline can be seen, probably reflecting the recent improvement in child health and safety.

Childhood-onset epilepsy five decades later. A prospective population-based cohort study.

OBJECTIVE: To study the impact of childhood-onset epilepsy on a variety of outcomes across the life span. METHODS: A population-based cohort of 245 subjects with childhood-onset epilepsy was assessed for outcomes at 45 years. In addition, 51 of 78 surviving subjects with uncomplicated epilepsy and 52 of 99 originally matched controls participated in a detailed evaluation including electroencephalography (EEG), imaging, and laboratory studies at 50 years. RESULTS: Of 179 surviving subjects, 61% were in terminal 10-year remission and 43% in remission off medications. At 45 years, 95% of the idiopathic group, 72% of the cryptogenic group, and 47% of the remote symptomatic group were in terminal remission (p < 0.001). Abnormal neurologic signs were significantly more common in subjects with uncomplicated epilepsy than in controls. Mortality during period 1992-2012 was higher in subjects than in controls (9% vs. 1%, p = 0.02). The rate of 3T MRI abnormalities was higher in subjects than in controls (risk ratio [RR] 2.0; 1.3-3.1) specifically including findings considered markers of cerebrovascular disease (RR 2.5; 1.04-5.9). Even subjects with idiopathic epilepsy had higher rates of imaging abnormalities than controls (73% vs. 34%, p = 0.002). SIGNIFICANCE: Long-term seizure outcomes are excellent and a function of etiology. The presence of imaging abnormalities suggestive of vascular disease may put these subjects at higher risk for clinically evident stroke and cognitive changes as they age.

Infantile colic associated with childhood migraine: A prospective cohort study.

PURPOSE: To explore the association between infantile colic and adolescent migraine. METHOD: In a randomized general population sample, families expecting their first child were prospectively followed for infantile colic and adolescent migraine. RESULTS: Colic was diagnosed in 160 (13%) of 1267 infants until the age of 3 months. Migraine was ascertained in 129 (16%) of 787 adolescents at age 18 years. History of infantile colic was identified in 96 (12%) of 787 adolescents and no such history in 658 (88%) of 787 adolescents. Migraine was present in 22 (23%)/96 adolescents who had a history of infantile colic, but in only 74 (11%)/658 ones who had no such history. Of the 22 adolescents, 14 (64%) had migraine without aura and eight (36%) had migraine with aura. Infants with colic had an almost three-fold risk (risk ratio 2.8, 95% confidence interval 1.2-6.5) for adolescent migraine without aura, but no increased risk for migraine with aura (0.8, 0.3-2.2). DISCUSSION AND CONCLUSIONS: Infantile colic seems to be associated with an increased risk for migraine without aura, but not for migraine with aura. Whether infantile colic per se is a type of infantile migraine or an antecedent of future migraine remains to be answered by further research.

Adolescent cervical disc degeneration in MRI does not predict adult headache or neck pain: A 5-year follow-up of adolescents with and without headache.

AIM: The impact of early degenerative changes of the cervical spine on pain in adulthood is unknown. The objective was to determine whether degeneration in adolescence predicts headache or neck pain in young adulthood. METHODS: As part of a follow-up of schoolchildren with and without headache, 17-year-old adolescents with headache at least three times a month (N = 47) and adolescents with no headache (N = 22) participated in a magnetic resonance imaging (MRI) study of the cervical spine. The same adolescents were re-examined by phone interview at the age of 22 years (N = 60/69, 87%). RESULTS: Mild disc degeneration at the age of 17 years was common, but was not associated with either frequent or intensive headache or neck pain at the age of 22 years. Conclusion: Mild degenerative changes of the cervical spine in 17-year-old adolescents cannot be regarded as a cause of future headache or neck pain.

Clinical conditions of long-term cure in childhood-onset epilepsy: a 45-year follow-up study.

Clinical conditions of long-term cure in childhood-onset epilepsy, defined as sustained remission off antiepileptic drug (AED) treatment, are not well known. To address that clinically important question, we determined clinical factors predictive of long-term seizure cure in a population-based cohort of 133 patients followed up since their first seizure before the age of 16 years. At the end of the 45-year follow-up (mean=39.8, median=44, range=11-47), 81 (61%) of the 133 patients had entered at least 5-year remission off AEDs, meeting our definition of cure. The 81 patients were seizure-free off AEDs for a mean of 34.4 (median=38, range=6-46) years and 59 (73%) of the 81 patients following the first standard medication until the end of follow-up (mean=36.5, median=39, range=14-46 years). Four independent factors were found to be associated with cure compared with having seizures while on AEDs: seizure frequency less than weekly during the first 12 months of AED treatment (p=0.002), pretreatment seizure frequency less than weekly (p=0.002), higher IQ (>70; p=0.021), and idiopathic or cryptogenic vs. symptomatic etiology (p=0.042). Patients with seizure frequency of less than once a week during early treatment and idiopathic etiology had a ninefold chance to of being cured since the onset of the first adequate antiepileptic therapy until the end of follow-up compared with patients who a symptomatic etiology had at least weekly seizures while on AEDs (RR=8.7, 95% CI=2.0-37.0; p<0.001). In conclusion, IQ, etiology, and seizure frequencies both in the first year of AED treatment and prior to medication appear to be clinical predictors of cure in childhood-onset epilepsy.

Dental fear affects adolescent perception of interaction with dental staff.

The main purpose of this study was to explore whether subjective perception of interaction with dental staff is associated with dental fear in a population-based sample of 18-yr-old adolescents (n = 773). The interaction was measured using the Patient Dental Staff Interaction Questionnaire (PDSIQ), validated with exploratory and confirmatory factor analyses, which yielded the factors of 'kind atmosphere and mutual communication', 'roughness', 'insecurity', 'trust and safety', and 'shame and guilt'. Dental fear was measured using the Modified Dental Anxiety Scale (MDAS). Gender and sense of coherence (SOC) were included as potential confounding variables. Adolescents with high dental fear more often perceived their interaction with dental staff negatively and more often felt insecure than others. This difference persisted after adjustment for gender and SOC. In conclusion, adolescents with high dental fear may perceive their interaction with dental staff more positively if the staff succeed in creating a positive, trusting, approving, and supportive atmosphere with kindness, calmness, and patience. The communication and interaction skills of dental staff may play a particularly important role when encountering highly fearful dental patients.

The changing incidence of childhood epilepsy in Finland.

INTRODUCTION: to investigate the childhood epilepsy incidence, population trends, associated factors, and validate the national population registers. METHODS: a comprehensive comparative analysis of childhood epilepsy in the population during two distinct time intervals using medical records, appropriate national medical and population registers, and two random samples for control. RESULTS: In 1961-1964, the average incidence of epilepsy was 38/100,000 and during 1991-2000 65.9 (95 % CI 59.6 to 72.2) and 65.6/100,000 person-years after adjustment for the European Standard Population. This increase was significant (p<0.0001) as was a decline (p<0.003) from 1991 to 1995 to 1996-2000. The decline in incidence for girls occurred at a younger age compared to boys. Epilepsy cases associated with prenatal and perinatal factors were 50 % lower in 1991-2000 than in 1961-1964, especially related to asphyxia, infections, pre-eclampsia, and imminent abortion. The national Register for Healthcare independently identified 94.5 % of relevant cases (University Hospital alone 81.2 %, and Drug Register alone 74.3 %). DISCUSSION: Over the past five decades, the incidence rate of childhood epilepsy has exhibited a dynamic pattern, with a notable increase until the 1990's, followed by a stabilization at an incidence rate of approximately 60-70 per 100,000 person-years. Our findings, in line with other recent Finnish research, support a significant decrease in incidence since the mid-1990's. The underlying reasons for the increase and decrease remain unclear. Finnish national registers for epilepsy have established themselves as highly dependable resources for conducting epidemiological research. CONCLUSION: Childhood epilepsy incidence in Finland is similar to other industrialized countries, but there are signs of a declining trend emerging.

Synchronous timing of return to breeding sites in a long-distance migratory seabird with ocean-scale variation in migration schedules.

BACKGROUND: Migratory birds generally have tightly scheduled annual cycles, in which delays can have carry-over effects on the timing of later events, ultimately impacting reproductive output. Whether temporal carry-over effects are more pronounced among migrations over larger distances, with tighter schedules, is a largely unexplored question. METHODS: We tracked individual Arctic Skuas Stercorarius parasiticus, a long-distance migratory seabird, from eight breeding populations between Greenland and Siberia using light-level geolocators. We tested whether migration schedules among breeding populations differ as a function of their use of seven widely divergent wintering areas across the Atlantic Ocean, Mediterranean Sea and Indian Ocean. RESULTS: Breeding at higher latitudes led not only to later reproduction and migration, but also faster spring migration and shorter time between return to the breeding area and clutch initiation. Wintering area was consistent within individuals among years; and more distant areas were associated with more time spent on migration and less time in the wintering areas. Skuas adjusted the period spent in the wintering area, regardless of migration distance, which buffered the variation in timing of autumn migration. Choice of wintering area had only minor effects on timing of return at the breeding area and timing of breeding and these effects were not consistent between breeding populations. CONCLUSION: The lack of a consistent effect of wintering area on timing of return between breeding areas indicates that individuals synchronize their arrival with others in their population despite extensive individual differences in migration strategies.

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.).