Self-reported quality of life and degree of youth-parent agreement: A long-term follow-up of childhood-onset epilepsy.

OBJECTIVE: To prospectively delineate self-reported health-related quality of life (HRQOL) of adolescents and young adults (AYAs) 8 and 10 years after an epilepsy diagnosis and evaluate the degree of AYA-parent agreement in ratings of AYA's HRQOL. METHODS: Data came from the Health-Related Quality of Life in Children with Epilepsy Study (HERQULES), a 10-year longitudinal study of children, aged 4-12 years, with newly diagnosed epilepsy. Epilepsy-specific HRQOL was self-reported by AYA 8 and 10 years after diagnosis and by parents at multiple time points throughout the 10-year follow-up. Measurers of HRQOL over time were analyzed using a linear mixed-effect model approach. AYA-parent agreement was evaluated using intraclass correlation coefficient (ICC) and Bland-Altman plots. RESULTS: A total of 165 AYAs participated at long-term follow-up. There was considerable heterogeneity among AYA's HRQOL, and as a group, there was no significant change in HRQOL from the 8- to 10-year follow-up. Household income at the time of diagnosis, seizure control at follow-up, and a history of emotional problems (anxiety/depression) were independent predictors of HRQOL at follow-up. AYA-parent agreement on AYA's HRQOL was moderate (ICC 0.62, 95% CI 0.51-0.71), although considerable differences were observed at the individual level. AYA-parent agreement varied with AYA's and parent's age, seizure control, and family environment. SIGNIFICANCE: In the long-term after a diagnosis of epilepsy, AYAs report stable HRQOL over time at the group level, although notable individual differences exist. Seizure control, anxiety/depression, and family environment meaningfully impact AYA's long-term HRQOL. AYA and parent reports on HRQOL are similar at the group level, although they cannot be used interchangeably, given the large individual differences observed.

Trajectories of quality of life 10 years following a diagnosis of epilepsy in childhood.

OBJECTIVE: This study estimated trajectories of health-related quality of life (HRQOL) over a 10-year period among children newly diagnosed with epilepsy. We also modeled the characteristics of children, parents, and families associated with each identified trajectory. METHODS: Data came from the HERQULES (Health-Related Quality of Life in Children With Epilepsy Study), a Canada-wide prospective cohort study of children (aged 4-12 years) with newly diagnosed epilepsy. Parents reported on their children's HRQOL at diagnosis, and at 0.5-, 1-, 2-, 8-, and 10-year follow-ups using the Quality of Life in Childhood Epilepsy Questionnaire-55. Trajectories of HRQOL were identified using latent class growth models. Characteristics of children, parents, and families at the time of diagnosis that were associated with each trajectory were identified using multinomial logistic regression. RESULTS: A total of 367 children were included. Four unique HRQOL trajectories were identified; 11% of the cohort was characterized by low and stable scores, 18% by intermediate and stable scores, 35% by intermediate scores that increased then plateaued, and 43% by high scores that increased then plateaued. Absence of comorbidities, less severe epilepsy, and better family environment (greater satisfaction with family relationships and fewer family demands) at the time of diagnosis were associated with better long-term HRQOL trajectories. Although the analyses used estimates for missing values and accounted for any nonrandom attrition, the proportion of children with poorer HRQOL trajectories may be underestimated. SIGNIFICANCE: Children with new onset epilepsy are heterogenous and follow unique HRQOL trajectories over the long term. Overall, HRQOL improves for the majority in the first 2 years after diagnosis, with these improvements sustained over the long term.

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.

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.

What do epileptologists recommend about discontinuing antiepileptic drugs for a second time in children?

OBJECTIVE: There is a broad consensus that antiepileptic drugs (AEDs) may be withdrawn after two years of seizure freedom for most children with epilepsy. If seizures recur and are, again, completely controlled with AEDs, little is known about discontinuing a second time. We surveyed American and Canadian pediatric epileptologists to understand their current practice. METHODS: In 2014, a survey was sent via e-mail to 193 pediatric epileptologists to learn about AED discontinuation practices in children. The survey asked direct questions about practice and posed five "real-life" cases where the decision to discontinue might be difficult. Participants were identified through membership lists of several US and Canadian epilepsy organizations. RESULTS: There were 94 (49%) completed surveys. Sixty-three participants had ≥ 10 years in practice ("more experienced": mean 23 ± 9 years), and 31 had < 10 years ("less experienced": mean 6 ± 2 ). Overall, 62% recommended AED discontinuation for the first time after 2-3 years of seizure freedom, and 61% recommended discontinuation for the second time after 2-3 years. Fifty-six percent of "more experienced" clinicians required a longer seizure-free period prior to a second discontinuation (p < 0.001) compared with 26% of "less experienced" clinicians (p = ns). Overall, most participants suggested an AED taper duration of 2-6 months for the first and second attempts, 52% and 68%, respectively. Both groups wean AEDs more slowly during the second attempt (p < 0.001). There was only 40-60% agreement among participants to discontinue AEDs in four of the cases. CONCLUSION: Nearly half (46%) of pediatric epileptologists require a longer seizure-free period the second time they attempt to discontinue AEDs compared with the first attempt and wean down AEDs somewhat more slowly. Although a variety of factors influence decision-making, there was a high level of disagreement to discontinue AEDs a second time in "real-life" cases.

Epidemiologic aspects: lost in transition.

Population-based studies focusing on the long-term prognosis of childhood-onset epilepsy show that despite seizure remission in 70-80% of cases, cognitive, behavioral and psychosocial complications are common and will require management and monitoring in adulthood. This type of study design also demonstrates that death is rare in children who are intellectually and neurologically normal and followed for many years, which is the same for the general population. Only those children with neurologic problems sufficiently severe to interfere with activities of daily living have an increased risk of death in childhood. Investigation of potentially remediable complications is paramount, and the use of antiepileptic medications with potential adverse cognitive and behavioral effects should be identified and eliminated or reduced. In addition, education of the family should be improved. As well, identification and control of social and psychiatric complications is necessary and implies a comprehensive management of the patient before and after the transition from childhood into adulthood.

Transition issues for benign epilepsy with centrotemporal spikes, nonlesional focal epilepsy in otherwise normal children, childhood absence epilepsy, and juvenile myoclonic epilepsy.

This chapter covers the syndromes of benign epilepsy with centrotemporal spikes (BECTS), nonlesional focal epilepsy in otherwise normal children (NLFN), and the genetic generalized epilepsies. BECTS is an epilepsy syndrome that always enters terminal remission before the general age of a planned transition of adolescents. This is also the case for the majority (65%) of those with childhood absence epilepsy (CAE). Approximately 15% of patients with CAE who initially remit during their childhood years later develop juvenile myoclonic epilepsy (JME) as teenagers. They will have many issues for continuing medical care and transition, because their seizure disorder generally persists into adulthood. A significant minority of NLFN (~35%) and most patients with JME continue to have active epilepsy into adulthood. In addition, CAE, JME, and NLFN patients are at risk of a number of significant adverse social outcomes that require ongoing advice and counseling.

The adult seizure and social outcomes of children with partial complex seizures.

Most intellectually normal children with focal epilepsy have partial complex or focal with secondary generalization seizures without a precise epilepsy syndrome. Their long-term outcome is largely unknown. Cases were identified from the population-based Nova Scotia Childhood Epilepsy cohort. Those eligible had seizure onset at 1 month to 16 years between 1977 and 1985, normal intelligence, ≥10 years of follow-up, only focal seizures and no benign epilepsy syndromes. There were 108 patients with partial complex with or without secondary generalization as the only seizure type(s) throughout (partial complex group) and 80 with secondary generalization as the only seizure type (secondary generalization group). Average age ± standard deviation at onset was 7.3 ± 4.5 years and follow-up was 27.9 ± 5.4 years. At follow-up, 57% of the partial complex group were in remission versus 81% of the secondary generalization group (P = 0.001). The partial complex group was more likely to be intractable or have undergone epilepsy surgery (36% versus 5%, P = 0.000). In the partial complex group, 28% had <5 years seizure free versus 5% in the secondary generalized group (P = 0.000). More patients in the partial complex group had undergone mental health assessments (59% versus 32%, P = 0.000), and 33% had a psychiatric diagnosis versus 15% in the secondary generalized group (P = 0.004). More patients with partial complex seizures had specific learning disorders (63% versus 45%, P = 0.03). Seven markers of poor social outcome were more common in patients with partial complex seizures (>2 markers: 34% versus 10%, P = 0.000). During 25-30 years of follow-up, >50% of intellectually normal patients with childhood-onset partial complex seizures had difficult-to-control seizures and learning and psychiatric/social problems. Most with secondary generalized seizures only had remission and better academic and psychiatric/social outcomes.

Trajectories of health-related quality of life in children with epilepsy: a cohort study.

PURPOSE: Little is known about subgroups of children with epilepsy who may experience less favorable outcomes over time. The objectives of this study were to document trajectories of health-related quality of life (HRQL) and to identify predictors of the trajectory group in children with new-onset epilepsy. METHODS: Data were obtained from the Health Related Quality of Life in Children with Epilepsy Study, a prospective multisite study of children 4-12 years old with new-onset epilepsy followed for 24 months. Health-related quality of life was measured using the Quality of Life in Childhood Epilepsy questionnaire. Trajectories of HRQL were investigated using latent class trajectory modeling. Multinomial logistic regression was used to identify child, parent, and family predictors of HRQL trajectories. KEY FINDINGS: A total of 374 families responded at baseline and 283 (76%) completed the study. Five HRQL trajectories were observed: low-increasing (4%), moderate-decreasing (12%), moderate-increasing (22%), high-increasing (32%), and high-stable (30%). Many children in the low-increasing, moderate-increasing, high-increasing, and high-stable had clinically meaningful improvements in HRQL: 82%, 47%, 63%, and 44%, respectively. In contrast, the majority of children in the moderate-decreasing group (56%) experienced clinically meaningful declines in their HRQL. Factors predicting trajectories were number of antiepileptic drugs prescribed, presence of comorbid behavior or cognitive problems, parent depression, and family functioning and demands. SIGNIFICANCE: Results suggested that children with epilepsy are not homogenous but rather consist of groups with different trajectories and unique predictors of HRQL. Problems associated with child behavior and cognition were the strongest predictors identified. Given that several risk factors are modifiable, it is important to examine these as potential targets within a family-centered framework to improve HRQL of children with new-onset epilepsy.

Epidemiology of juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a widely recognized presumed genetic, electroclinical idiopathic generalized epilepsy syndrome. The prevalence of JME in large cohorts has been estimated to be 5% to 10% of all epilepsies and around 18% of idiopathic generalized epilepsies but may be lower in some settings. There is a marked female predominance. However, some of the basic epidemiology of JME is not well known, possibly because the syndrome is not sharply defined. A questionnaire study about the diagnostic criteria for JME suggests that diagnosis of JME can be made with the history of myoclonus plus a single generalized tonic-clonic seizure plus generalized fast spike-waves or polyspike-waves on the EEG. However, until these diagnostic criteria are fully accepted, the detailed epidemiology of JME will remain imprecise.

Lifetime prognosis of juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is among the most common types of genetic epilepsies, displaying a good prognosis when treated with appropriate drugs, but with a well-known tendency to relapse after withdrawal. The majority of patients with JME have continuing seizures after a follow-up of two decades. However, 17% are able to discontinue medication and remain seizure-free thereafter. Clinicians should remember that there is a small but still considerable subgroup of JME patients whose seizures are difficult to treat before informing patients with newly-diagnosed JME about their "benign" prognosis. This resistant course is not fully explained, though there are many suggested factors. The dominating myoclonic seizures disappear or diminish in severity in the fourth decade of life. Despite the favorable seizure outcome in most of the cases, 3/4 of patients with JME have at least one major unfavorable social outcome. The possible subsyndromes of JME, its genetic background, and its pathophysiological and neuroimaging correlates should be further investigated.

Dietary therapies for epilepsy: future research.

Since 1921, dietary therapies have remained valuable options in the treatment of intractable childhood epilepsy. The traditional ketogenic diet has been well demonstrated, including in a recent randomized, controlled trial, as being highly effective. More recent alternative diets such as the medium-chain triglyceride diet, modified Atkins diet, and low-glycemic-index treatment have expanded the use of this modality to more children as well as adults. In this review, we discuss our top 10 most pressing research topics related to the ketogenic diet that warrant future study. As well, two promising ketogenic diet clinical researchers discuss their past and current research to help answer some of these questions.

The relation between children's pain behaviour and developmental characteristics: a cross-sectional study.

AIM: To determine whether children with developmental disabilities show responses to pain that vary according to developmental level. METHOD: Factor analytical methods were used to explore whether pain behaviour is independent of developmental characteristics. As part of a longitudinal study, caregivers of 123 children (67 males, 56 females; age range 40 mo-21 y 6 mo) completed the Non-communicating Children's Pain Checklist-Revised (NCCPC-R), the Vineland Adaptive Behavior Scales, Second Edition (VABS-II), and the Pediatric Evaluation of Disability Inventory (PEDI). Deviation intelligence quotients (DIQs) were also generated. Two varimax rotated principal components analyses (PCAs) included the NCCPC-R subscales, DIQs, and age. One also included VABS-II subdomain scores and the other, PEDI scores, to allow examination of whether pain and developmental scores produced distinct components to evaluate the independence of pain behaviour from developmental factors. RESULTS: Children's mean age equivalents on the VABS-II were: Communication (36.4 mo, SD 34.8), Daily Living Skills (31.8 mo, SD 35.9), Socialization (43.2 mo, SD 49.9), and Motor Skills (21.6 mo, SD 20.3). Pain behaviour was distinct from developmental characteristics. The PCA including the VABS-II accounted for 78.4% of variance, with four components: Developmental Level, Pain Behaviour, Motor Development, and Chronological Age. The PCA that included the PEDI accounted for 69.4% of variance, with three corresponding components: Pain Behaviour, Developmental Level, and Chronological Age. INTERPRETATION: Pain behaviour was distinct from developmental factors in two separate analyses using two functional measures. Clinicians can be confident that pain assessment with the NCCPC-R is not affected by children's developmental level.

Evaluation of the responsiveness of the Impact of Pediatric Epilepsy Scale.

The Impact of Pediatric Epilepsy Scale (IPES) is an epilepsy-specific, health-related quality of life (HRQOL) questionnaire that is brief, accurate, and valid and assesses the influence of epilepsy on the child and family. This study prospectively investigates the responsiveness of the IPES, 3 years after the IPES questionnaire was initially validated. The same parents or caregivers completed the IPES. Changes in IPES scores were compared with changes in epilepsy severity. IPES Total scores were highly related to change in seizure severity (Wilks' lambda F (3, 11)=5.0, P<0.001). Those whose seizure severity decreased had decreased IPES scores (indicating improvement of HRQOL); those with increased seizure severity had increased IPES scores and reported poorer HRQOL; and those with no change in seizure severity had no change in the IPES score and no change in HRQOL. In conclusion, the IPES is useful for measurement of a child's epilepsy-specific HRQOL during treatment and is responsive to changes in epilepsy severity over time.

Coping with a child with Dravet syndrome: insights from families.

Dravet syndrome is a truly catastrophic childhood-onset epilepsy. Families are faced with repeated episodes of status epilepticus, intractable seizures, mental handicap, behavior disorders, and a life of dependency; understandably, coping with Dravet syndrome is very difficult. Twenty-four families with a child with Dravet syndrome were interviewed and identified some practical suggestions to improve their daily life. These included inserting an indwelling venous access device, creating a portable microenvironment, writing an emergency department protocol, establishing emergency routines for the family, assigning a parent on call to lessen the effect on siblings, creating personal time to decrease parental stress, finding respite care, and contacting an Internet support group. Unresolved and common issues included transition to adult care, the utility of early diagnosis, and social isolation. These solutions and issues may be helpful to many families with a child with Dravet syndrome and possibly other severe childhood-onset epilepsies.

Stigma of epilepsy.

Epilepsy directly affects 50 million people worldwide. Most can achieve excellent seizure control; however, people living with epilepsy continue to suffer from enacted or perceived stigma that is based on myths, misconceptions and misunderstandings that have persisted for thousands of years. This paper reviews the frequency and nature of stigma toward epilepsy. Significant negative attitudes prevail in the adolescent and adult public worldwide leading to loneliness and social avoidance both in school and in the workplace. People with epilepsy are often wrongly viewed as having mental health and antisocial issues and as being potentially violent toward others. Twenty-five percent of adults having epilepsy describe social stigma as a result of their epilepsy. They fear rejection and often feel shame or loneliness from this diagnosis. The psychosocial and social impact of epilepsy is significant. Yet few specific interventions have been demonstrated to alter this perception. The effect on public education is primarily short-term, while change over the long-term in attitudes and inaccurate beliefs have not presently been proven effective. School education programming demonstrates improved knowledge and attitude a month after a classroom intervention, but persisting change over a longer period of time has not been evaluated. In-depth adult psycho-educational programs for adults with epilepsy improves knowledge, coping skills and level of felt stigma. However these gains have not demonstrated persistence over time. Myths, misconceptions and misunderstandings about epilepsy continue and programs aimed at increasing knowledge and reducing negative public attitudes should be enhanced.

Successful neurological outcome of a child with classical phenylketonuria and acute lymphoblastic leukemia: a 7-year follow-up.

We report on the medical management and outcome of a child with classical phenylketonuria (PKU) who developed acute lymphoblastic leukemia (ALL). Chemotherapy began at 24 months of age. Initial problems associated with treatment lead to remarkable releases of phenylalanine, a neurotoxin. Causes included increased catabolism secondary to tumor lysis and chemotherapy, as well as infection, intermittent fasting and anorexia. Medical management involved daily monitoring of Phe levels and major changes in the amount of medical formula and the intake of protein containing foods in the diet. The child is currently in remission from ALL and has a normal neurodevelopmental outcome 7 years after the ALL diagnosis.

People with epilepsy are often perceived as violent.

This study explores the possibility that people with epilepsy are commonly and persistently perceived as potentially violent during and between seizures. In 1981 and again in 2006, we assessed responses to a questionnaire that includes vignettes and direct questions about violence in epilepsy. Groups sampled were medical and law students, physicians, child care workers, the general public, and people with epilepsy (n=271 in 1981 and n=388 in 2006). Nearly half of the respondents believed that violence was possible or likely during a seizure. Almost all groups answered at least 40% of questions incorrectly; the exception was physicians, who answered 20% incorrectly. Responses were fairly stable over the 25-year interval. Logistic regression revealed few predictors: older responders and physicians had more correct answers, whereas law students had poorer performance. These results indicate that fear of violence at the hands of people with epilepsy is prevalent and may contribute to stigma.

Psychometric properties of the non-communicating children's pain checklist-revised.

The non-communicating children's pain checklist (NCCPC) has displayed preliminary validity and reliability for measuring pain in children with severe cognitive impairments (Dev Med Child Neurol 42 (2000) 609). This study provides evidence of the psychometric properties of a revised NCCPC (NCCPC-R) with a larger cohort of children. Caregivers of 71 children with severe cognitive impairments (aged 3-18) conducted observations of their children using the NCCPC-R during a time of pain and a time without pain. Fifty-five caregivers completed a second set of observations. The score results on the NCCPC-R were: internally consistent, significantly related to pain intensity ratings provided by caregivers, consistent over time, sensitive to pain, and specific to pain. Analyses of children's individual scores indicated up to 95% of their scores were consistent. Receiver operating characteristic curves suggest a score of 7 or greater on the NCCPC-R as indicative of pain in children with cognitive impairments, with 84% sensitivity and up to 77% specificity. These results provide evidence of NCCPC-R having excellent psychometric properties.