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.

Acute symptomatic seizures: an educational, evidence-based review.

Acute symptomatic seizures occurring in close temporal relationship with an acute CNS insult are distinct from epilepsy and occur frequently in clinical practice. The aim of this educational review is to provide information on the most important aspects related to acute symptomatic seizures that will allow clinicians to accurately distinguish acute symptomatic seizures from epilepsy in their patients. We explain the definition of acute symptomatic seizures and we illustrate how acute symptomatic seizures differ from epilepsy. We describe acute symptomatic seizures in the context of their various underlying aetiologies and we discuss the approach to the management of patients with acute symptomatic seizures.

What Do We Need to Know About Transition/Transfer Programs and What Sort of Research Will Answer the Questions?

Despite an increasing literature, there are many unanswered questions about transition to adult care for youth with chronic disorders. This paper questions the definition and components of optimal transition programs, their effectiveness and costs. Few transition programs have been comprehensively evaluated and effectiveness studies are usually based on a historical control group. Transition clinics for neurological disorders are described but not evaluated. Studies in diabetes, renal transplant, and rheumatologic disorders provide the best available evidence, albeit limited, of the value of transition clinics/programs. A few studies have addressed the cost of transition clinics and suggest that the incremental costs of the clinic are recouped by reduced medical costs in adult care. There is room for a great deal more research about transition.

Childhood epilepsy with a small number of seizures may be left untreated: an international prospective study.

It is unknown whether treatment with antiepileptic drugs in children with epilepsy with a presumed good prognosis is always necessary. We aimed to study the course of newly diagnosed epilepsy in children with a presumed good prognosis who are managed without AED treatment. A total of 151 children (one month to 12 years of age) with two to five lifetime unprovoked seizures (excluding febrile convulsions), were followed for three years. Treatment was initially withheld. Children with symptomatic epilepsy, or absence or myoclonic epilepsy, were excluded. AED treatment was started after >10 lifetime seizures or an episode of status epilepticus during follow-up, or if the parents or treating physician deemed it otherwise necessary. During follow-up, 113 children continued to meet our criteria for refraining from treatment with antiepileptic drugs, yet 30 started treatment at the request of the parents. Thirty-eight children at some time met the criteria to start treatment, but the parents of 16 declined treatment. In all, 99 (66%) children maintained the no-treatment regime. Ninety-eight children (65% of 151) reached terminal remission for at least one year, including 83 who did not receive antiepileptic drug treatment (84% of the untreated 99). Mean terminal remission was significantly longer in the group with a total of <10 seizures compared to those with >10 seizures. Treatment did not increase the length of terminal remission. Adverse events, including traumatic injury, occurred equally in the treated and untreated children. Measures of quality of life suggested a better outcome in those without treatment. Children with newly diagnosed epilepsy with a presumed good prognosis may not need immediate AED treatment. Postponing treatment does not alter the chance of remission or the risk of accidents and adverse events and appears to be associated with a good quality of life.

The evaluation and costs of transition programs for youth with epilepsy.

There is limited information about the effectiveness of transition programs for youth moving from pediatric to adult care with any chronic disease. Two Delphi studies and National Institute for Health and Care Excellence (NICE) guidelines about transition for epilepsy have suggested few critical outcome measures for transition. A single large prospective study found that the most important transition program elements were appropriate parent involvement, promotion of health self-efficacy, and meeting the adult team before transfer. Two Cochrane reviews of the value of transition for epilepsy found insufficient evidence to establish or refute the value of various programs, although evaluation of a few programs suggested a great deal of family/patient satisfaction. The cost of transition programs and their cost effectiveness have also not been established except for renal transplantation where transition programs were associated with fewer losses of the transplanted kidneys, a cost-effective outcome. Published data on the overall cost of care for children and adults with epilepsy may be helpful to establish a business plan for a transition program, and are briefly reviewed. Establishing cost effectiveness of transition programs for epilepsy would promote their establishment and viability. However, a number of studies will be needed based on the nature of the program, the healthcare system where it is carried out, and the type of epilepsy. In fee-for-service health systems, the reevaluation of patients with epilepsy prior to transfer may be sufficient to cover the costs of the transition program, whereas in single payer systems, there may be positive downstream health or societal benefits that justify the costs. A theoretical framework for comprehensive evaluation of epilepsy transition programs is needed. The Triple Aim Framework seems applicable with focus on population health, patient experiences, and cost and has the potential to assess transition interventions in the context of system-wide improvements in healthcare. Transition programs in general have not been well evaluated, and very little evaluation data exist regarding transition programs for epilepsy. We recommend more evaluative research using rigorous methodology to comprehensively assess these programs.

How can transition to adult care be best orchestrated for adolescents with epilepsy?

Objective evidence is limited for the value of transition programs for youth with chronic illness moving from pediatric to adult care; however, such programs intuitively "make sense". We describe the strengths and weaknesses of a variety of transition programs from around the world for adolescents with epilepsy. Consequences of poorly organized transition beyond suboptimal seizure control may include an increased risk of sudden unexpected death in epilepsy (SUDEP), poor psychological and social outcome, and inadequate management of comorbidities. The content of transition programs for those with normal intelligence differs from those with intellectual disability, but both groups may benefit from an emphasis on sporting activities. Concerns that may interfere with optimal transition include lack of nursing or social work services, limited numbers of adult neurologists/epileptologists confident in the treatment of complex pediatric epilepsy problems, institutional financial support, and time constraints for pediatric and adult physicians who treat epilepsy and the provision of multidisciplinary care. Successful programs eventually need to rely on a several adult physicians, nurses, and other key healthcare providers and use novel approaches to complex care. More research is needed to document the value and effectiveness of transition programs for youth with epilepsy to persuade institutions and healthcare professionals to support these ventures.

Regression in children with epilepsy.

Regression in children with epilepsy may involve loss of cognitive abilities, failure to progress or a slowing of developmental trajectory. A few seizures do not lead to regression. Large numbers of seizures may be associated with regression but the cause is an important cofounder. Individual spike discharges on EEG are associated with transient cognitive impairment and continuous spike discharges with regression. Regression may be global in continuous spike wave in slow sleep (CSWS) or specific (auditory agnosia) in Landau Kleffner syndrome. Regression is mild and transient in Rolandic Epilepsy or profound and permanent in West Syndrome. Epilepsy syndromes grouped under "epileptic encephalopathies" may lead to regression, although proof of this concept is not strong for many syndromes. The absence of cognitive assessment before epilepsy onset, the contribution of the cause and complications of treatment make for difficult methodological problems. The large majority of children with epilepsy do not have regression. There is need for more longitudinal studies of children with epileptic encephalopathies and other epilepsies associated with regression.

Cognitive Disabilities and Long-term Outcomes in Children with Epilepsy: A Tangled Tail.

Cognitive problems ranging from mild specific learning problems to profound intellectual disability (ID) are very common in children with epilepsy. For most affected patients there is good evidence that the cognitive problems are present at the onset of seizures and do not deteriorate over time. There is no evidence that a few seizures lead to cognitive deterioration. An exception may occur in children with epileptic encephalopathies, although this contention is not always easy to prove. ID is a strong predictor of intractable epilepsy, and the greater the degree of the ID the greater the risk of medication resistant epilepsy. It is not known if specific learning disorders are associated with more severe epilepsy. Rolandic epilepsy is unusual because possibly one-third of patients have transient cognitive and behavioral difficulties during the active phase but later have normal adult social outcome. More longitudinal studies with baseline and repeated cognitive assessments are needed to fully understand the relationship of cognitive problems to childhood onset epilepsy.

Epilepsy as a Network Disorder (1): What can we learn from other network disorders such as autistic spectrum disorder and mood disorders?

Epilepsy is a neurologic condition which often occurs with other neurologic and psychiatric disorders. The relation between epilepsy and these conditions is complex. Some population-based studies have identified a bidirectional relation, whereby not only patients with epilepsy are at increased risk of suffering from some of these neurologic and psychiatric disorders (migraine, stroke, dementia, autism, depression, anxiety disorders, Attention deficit hyperactivity disorder (ADHD), and psychosis), but also patients with these conditions are at increased risk of suffering from epilepsy. The existence of common pathogenic mechanisms has been postulated as a potential explanation of this phenomenon. To reassess the relationships between neurological and psychiatric conditions in general, and specifically autism, depression, Alzheimer's disease, schizophrenia, and epilepsy, a recent meeting brought together basic researchers and clinician scientists entitled "Epilepsy as a Network Disorder." This was the fourth in a series of conferences, the "Fourth International Halifax Conference and Retreat". This manuscript summarizes the proceedings on potential relations between Epilepsy on the one hand and autism and depression on the other. A companion manuscript provides a summary of the proceedings about the relation between epilepsy and Alzheimer's disease and schizophrenia, closed by the role of translational research in clarifying these relationships. The review of the topics in these two manuscripts will provide a better understanding of the mechanisms operant in some of the common neurologic and psychiatric comorbidities of epilepsy.

Intractable seizures after a lengthy remission in childhood-onset epilepsy.

OBJECTIVES: To establish the risk of subsequent intractable epilepsy after ≥2, ≥5, and ≥10 years of remission in childhood-onset epilepsy. METHODS: From the Nova Scotia childhood-onset epilepsy population-based cohort patients with all types of epilepsy were selected with ≥20 years follow-up from seizure onset (incidence cases). Children with childhood absence epilepsy were excluded. The rate of subsequent intractable epilepsy was then studied for patients with ≥5 years remission on or off AED treatment and compared with the rate for those with ≥2 and ≥10 years of remission. RESULTS: Three hundred eighty-eight eligible patients had ≥20 years follow-up (average 27.7 ± (standard deviation) 4 years) until they were an average of 34 ± 6.5 years of age. Overall, 297 (77%) had a period of ≥5 years of seizure freedom (average 21.2 ± 8 years), with 90% of these remissions continuing to the end of follow-up. Seizures recurred in 31 (10%) and were intractable in 7 (2%). For the 332 with a remission of ≥2 years seizure-free, 6.9% subsequently developed intractable epilepsy (p = 0.001). For the 260 with ≥10 years remission, 0.78% subsequently developed intractable epilepsy (p = 0.25 compared with ≥5 years remission). SIGNIFICANCE: Even after ≥5 or ≥10 years of seizure freedom, childhood-onset epilepsy may reappear and be intractable. The risk is fortunately small, but for most patients it is not possible to guarantee a permanent remission.

Epilepsy: Transition from pediatric to adult care. Recommendations of the Ontario epilepsy implementation task force.

The transition from a pediatric to adult health care system is challenging for many youths with epilepsy and their families. Recently, the Ministry of Health and Long-Term Care of the Province of Ontario, Canada, created a transition working group (TWG) to develop recommendations for the transition process for patients with epilepsy in the Province of Ontario. Herein we present an executive summary of this work. The TWG was composed of a multidisciplinary group of pediatric and adult epileptologists, psychiatrists, and family doctors from academia and from the community; neurologists from the community; nurses and social workers from pediatric and adult epilepsy programs; adolescent medicine physician specialists; a team of physicians, nurses, and social workers dedicated to patients with complex care needs; a lawyer; an occupational therapist; representatives from community epilepsy agencies; patients with epilepsy; parents of patients with epilepsy and severe intellectual disability; and project managers. Three main areas were addressed: (1) Diagnosis and Management of Seizures; 2) Mental Health and Psychosocial Needs; and 3) Financial, Community, and Legal Supports. Although there are no systematic studies on the outcomes of transition programs, the impressions of the TWG are as follows. Teenagers at risk of poor transition should be identified early. The care coordination between pediatric and adult neurologists and other specialists should begin before the actual transfer. The transition period is the ideal time to rethink the diagnosis and repeat diagnostic testing where indicated (particularly genetic testing, which now can uncover more etiologies than when patients were initially evaluated many years ago). Some screening tests should be repeated after the move to the adult system. The seven steps proposed herein may facilitate transition, thereby promoting uninterrupted and adequate care for youth with epilepsy leaving the pediatric system.

Understanding Death in Children With Epilepsy.

Death in children with epilepsy is profoundly disturbing, with lasting effects on the family, community, and health care providers. The overall risk of death for children with epilepsy is about ten times that of the general population. However, the risk of premature death for children without associated neurological comorbidities is similar to that of the general population, and most deaths are related to the cause of the epilepsy or associated neurological disability, not seizures. The most common cause of seizure-related death in children with epilepsy is sudden unexpected death in epilepsy (SUDEP). SUDEP is relatively uncommon in childhood, but the risk increases if epilepsy persists into adulthood. Although the direct cause of SUDEP remains unknown, most often death follows a generalized convulsive seizure and the risk of SUDEP is strongly related to drug-resistant epilepsy and frequent generalized tonic-clonic seizures. The most effective SUDEP prevention strategy is to reduce the frequency of seizures, although a number of seizure detection devices are under development and in the future may prove to be useful for seizure detection for those at particularly high risk. There are distinct benefits for health care professionals to discuss mortality with the family soon after the diagnosis of epilepsy. An individual approach is appropriate. When a child with epilepsy dies, particularly if the death was unexpected, family grief may be profound. Physicians and other health care professionals have a critical role in supporting families that lose a child to epilepsy. This review will provide health care providers with information needed to discuss the risk of death in children with epilepsy and support families following a loss.

Treatment issues for children with epilepsy transitioning to adult care.

This is the third of three papers that summarize the second symposium on Transition in Epilepsies held in Paris in June 2016. This paper focuses on treatment issues that arise during the course of childhood epilepsy and make the process of transition to adult care more complicated. Some AEDs used during childhood, such as stiripentol, vigabatrin, and cannabidiol, are unfamiliar to adult epilepsy specialists. In addition, new drugs are being developed for treatment of specific childhood onset epilepsy syndromes and have no indication yet for adults. The ketogenic diet may be effective during childhood but is difficult to continue in adult care. Regional adult epilepsy diet clinics could be helpful. Polytherapy is common for patients transitioning to adult care. Although these complex AED regimes are difficult, they are often possible to simplify. AEDs used in childhood may need to be reconsidered in adulthood. Rescue medications to stop prolonged seizures and clusters of seizures are in wide home use in children and can be continued in adulthood. Adherence/compliance is notoriously difficult for adolescents, but there are simple clinical approaches that should be helpful. Mental health issues including depression and anxiety are not always diagnosed and treated in children and young adults even though effective treatments are available. Attention deficit hyperactivity disorder and aggressive behavior disorders may interfere with transition and successful adulthood but these can be treated. For the majority, the adult social outcome of children with epilepsy is unsatisfactory with few proven interventions. The interface between pediatric and adult care for children with epilepsy is becoming increasingly complicated with a need for more comprehensive transition programs and adult epileptologists who are knowledgeable about special treatments that benefit this group of patients.

The transition from pediatric to adult care for youth with epilepsy: Basic biological, sociological, and psychological issues.

Transition from pediatric to adult health care for adolescents with epilepsy is challenging for the patient, family, and health care workers. This paper is the first of three that summarize the main findings from the 2nd Symposium on Transition in Epilepsies, held in Paris from June 14-25, 2016. In this paper we describe five basic themes that have an important effect on transition. First, there are important brain changes in adolescence that leave an imbalance between risk taking and pleasure seeking behaviors and frontal executive function compared with adults. Second, puberty is a major change during the transition age. The three most important but separate neuroendocrine axes involved in puberty are gonadarche (activation of the gonads), adrenarche (activation of adrenal androgen production), and activation of the growth hormone-insulin like growth factor. Third, sexual debut occurs during the transition years, and at an earlier age in adolescents with epilepsy than controls. Adult sexual performance is often unsatisfactory. Although AED-induced alterations in sexual hormones and temporal lobe epilepsy may play a role in hyposexuality, depression, anxiety, and other social factors appear most important. Fourth, psychological development is very important with an evolution from an early stage (ages 10-13years) with concrete thinking, to a middle stage (ages 14-17) with analytic and more abstract introspective thinking, and then to a late stage (ages 18-21) with at least the beginnings of adult reasoning. Epilepsy may derail this relatively orderly progression. Adolescents with autistic spectrum disorder may present with severe behavior problems that are sometimes related to undiagnosed epilepsy. Fifth, bone health in adolescence is critical to establish adequate mineralization for all of adult life. While AED interference with Vitamin D metabolism is important, there is evidence that the effects of AEDs on bone are more complex and involve changes in remodeling. Hence, some non-inducing AEDs may have a significant effect on bone health. All five of these themes lead to recommendations for how to approach adolescents and young adults during transition and some specific interventions to achieve maximum long-term adult independence and quality of life.

Poor versus rich children with epilepsy have the same clinical course and remission rates but a less favorable social outcome: A population-based study with 25 years of follow-up.

OBJECTIVE: To explore the influence of several estimates of family socioeconomic status on the long-term clinical course and social outcomes of children with epilepsy. METHODS: The Nova Scotia childhood epilepsy cohort is population based and includes all children in this Canadian province who developed epilepsy between 1977 and 1985. Eligible patients had ≥10 years of follow-up. Children with childhood absence epilepsy were excluded. Total family income at seizure onset was assessed at seizure onset and classified as "poor" (first quintile), "adequate" (second to third quintiles), and "well-off" (fourth to fifth quintiles). We also assessed parental education and home ownership. Social outcome was assessed in those with normal intelligence who were ≥18 years of age at the end of follow-up using a semistructured interview that explored eight adverse effects. RESULTS: Of 584 patients, 421 (72%) were included. Average follow-up was 26 ± 5.6 years. Overall 137 families (33%) had "poor" income, 159 (38%) had "adequate income," and 125 (30%) were "well-off." Terminal remission of epilepsy occurred in 65% of the poor, 61% of the adequate, and 61% of the well-off (p = ns). Intractable epilepsy, status epilepticus, number of antiepileptic drugs (AEDs) used, and the number of generalized tonic-clonic or focal with secondary generalization seizures through the clinical course was the same in all groups. Home ownership did not predict remission. Neither paternal nor maternal education was associated with remission. Poor children had significantly more adverse social outcomes including failure to graduate from high school, unemployment, personal poverty, inadvertent pregnancy, and psychiatric diagnoses. SIGNIFICANCE: In Nova Scotia with universal health care, coming from a poor or more affluent family does not seem to affect the clinical course or long-term seizure outcome of childhood epilepsy. Unfortunately children from poor families are less likely to have a good social outcome.

The neurologist's role in supporting transition to adult health care: A consensus statement.

The child neurologist has a critical role in planning and coordinating the successful transition from the pediatric to adult health care system for youth with neurologic conditions. Leadership in appropriately planning a youth's transition and in care coordination among health care, educational, vocational, and community services providers may assist in preventing gaps in care, delayed entry into the adult care system, and/or health crises for their adolescent patients. Youth whose neurologic conditions result in cognitive or physical disability and their families may need additional support during this transition, given the legal and financial considerations that may be required. Eight common principles that define the child neurologist's role in a successful transition process have been outlined by a multidisciplinary panel convened by the Child Neurology Foundation are introduced and described. The authors of this consensus statement recognize the current paucity of evidence for successful transition models and outline areas for future consideration.

Helping Families Cope with the Severe Stress of Dravet Syndrome.

A child with Dravet syndrome shakes family life to the core. Dravet syndrome usually has three phases: (1) up to 1-1½ years: with episodes of febrile status epilepticus but normal development; (2) age 1½ to ~6-10 years: with frequent seizures of varying types, developmental stagnation, behavioural and sleep problems; (3) after ~10 years: improvement in seizures, deteriorating gait, intellectual disability but some developmental gains. Complete seizure control is rare-simply prescribing medication is inadequate to help families. Based on structured interviews with 24 families and confirmed by more informal discussions with other families, we suggest strategies for coping with this catastrophe. A child with Dravet syndrome usually means that one parent cannot work-financial pressures should be anticipated. In Stage 1, the approach to status should include a written protocol. An indwelling catheter for rapid venous access may be helpful. In Stage 2, assistance finding qualified babysitters is required, and the extended family needs encouragement to help. Appropriate equipment, rescue medication and protocols should travel with the child. Siblings may benefit from a system of one parent "on call." An internet support group provides an invaluable lifeline. In Stage 3, family isolation may be extreme-respite care and personal time for parents are important. Death from status, accidents and SUDEP (sudden unexplained death in epilepsy) occurs in 15%. Fear of SUDEP needs to be addressed. Moving from paediatric to adult care is frightening; an epilepsy transition clinic is useful. Attention to these realities may improve the quality of life for both child and family.