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.

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 children with diffuse cortical malformations, multifocal postnatal lesions, (infectious and traumatic) and Lennox-Gastaut and similar syndromes.

Patients with epilepsy may have diffuse, serious brain disorders including genetically determined, multilobar malformations, traumatic brain injury, encephalitis and meningitis, and the many causes of Lennox-Gastaut syndrome. Transition to adult care needs to consider concomitant intellectual disability, refractory epilepsy, underlying cause, and other nonneurologic but significant problems, especially for genetic etiologies. Adult epilepsy care coupled with dedicated primary/family care is essential. A multidisciplinary setting may be optimal to address the many issues of clinical care, decision making, custody, and ongoing supervision.

What happens to children with epilepsy when they become adults? Some facts and opinions.

BACKGROUND: The adult outcome after childhood onset epilepsy is a complex subject because seizure types and severity are diverse, comorbidities are common, and additional factors influence social outcome. We review selected data about seizure remission or persistence and social outcome in adulthood. METHODS: Information came from published literature, especially population-based studies. RESULTS: In general, approximately 50-60% of children with epilepsy eventually have complete seizure remission (i.e., seizure free and off antiepileptic drug treatment): with longer follow-up, the remission rate improves. Predicting remission, persistent or intractable epilepsy is often inaccurate for an individual patient. A tiny proportion of children with epilepsy die as the result of seizures or sudden unexpected death in epilepsy patients; however, an otherwise normal child has the same risk of death as the reference population. When uncontrolled epilepsy persists into adulthood, the rate of sudden unexpected death in epilepsy patients possibly increases. Reports about social outcome in adulthood are increasing. For those with intellectual disability, a lifetime of dependency is to be expected. For those with normal intelligence, adult life is often unsatisfactory with high rates of incomplete education, unemployment, poverty, social isolation, inadvertent pregnancy, and psychiatric disorders. Seizure remission does not ensure good adult social outcome. CONCLUSIONS: Although seizure control in childhood is important, anticipating poor social outcome in adulthood may allow earlier interventions. A well-orchestrated transition from pediatric to adult health care may be beneficial for the 40-50% with persistent seizures and for the majority who are at risk for adult social difficulties.

Rolandic epilepsy has little effect on adult life 30 years later: a population-based study.

OBJECTIVE: To establish the adult social outcome for childhood-onset rolandic epilepsy. METHODS: Patients with medication-treated rolandic epilepsy were identified from the Nova Scotia prospective population-based cohort of childhood-onset epilepsy. Epilepsy onset was in 1977-1985 and follow-up was in 2010-2013 with chart review plus structured telephone interview for those older than 21 years. RESULTS: Forty-two children developed rolandic epilepsy (6% of 692 incident epilepsy cases in the cohort). Thirty-two (76%) were contacted when they were older than 21 years. Epilepsy onset averaged 7.7 ± 2.3 years, follow-up 29.5 ± 2.8 years, and final age 37 ± 3.4 years. All had epilepsy remission and were off antiepileptic drug treatment for 21.4 ± 6.6 years. There were 2 minor injuries from seizures and only 1 death (from a snowmobile accident). Overall, 41% had ≥ 1 of 7 adverse social outcomes, 6 had 1, 4 had 2, and 3 had ≥ 3. These were failure to complete high school (n = 7), pregnancy outside of a stable relationship (<6 months) (n = 7), depression or other psychiatric diagnosis (n = 3), unemployment (n = 1), living alone (n = 5), never in a romantic relationship >3 months (n = 1), and poverty (n = 2). Those who did not complete high school were more likely to have parents with low academic achievement and/or low income (p < 0.02). By comparison, rates of ≥ 1 adverse social outcomes for other epilepsies with normal intelligence from this cohort varied from 62% to 76%. CONCLUSIONS: The adult social outcome for children with rolandic epilepsy is remarkably better than for those with other major epilepsies and normal intelligence.

Mortality risks in new-onset childhood epilepsy.

OBJECTIVES: Estimate the causes and risk of death, specifically seizure related, in children followed from onset of epilepsy and to contrast the risk of seizure-related death with other common causes of death in the population. METHODS: Mortality experiences from 4 pediatric cohorts of newly diagnosed patients were combined. Causes of death were classified as seizure related (including sudden unexpected death [SUDEP]), natural causes, nonnatural causes, and unknown. RESULTS: Of 2239 subjects followed up for >30 000 person-years, 79 died. Ten subjects with lethal neurometabolic conditions were ultimately excluded. The overall death rate (per 100 000 person-years) was 228; 743 in complicated epilepsy (with associated neurodisability or underlying brain condition) and 36 in uncomplicated epilepsy. Thirteen deaths were seizure-related (10 SUDEP, 3 other), accounting for 19% of all deaths. Seizure-related death rates were 43 overall, 122 for complicated epilepsy, and 14 for uncomplicated epilepsy. Death rates from other natural causes were 159, 561, and 9, respectively. Of 48 deaths from other natural causes, 37 were due to pneumonia or other respiratory complications. CONCLUSIONS: Most excess death in young people with epilepsy is not seizure-related. Mortality is significantly higher compared with the general population in children with complicated epilepsy but not uncomplicated epilepsy. The SUDEP rate was similar to or higher than sudden infant death syndrome rates. In uncomplicated epilepsy, sudden and seizure-related death rates were similar to or higher than rates for other common causes of death in young people (eg, accidents, suicides, homicides). Relating the risk of death in epilepsy to familiar risks may facilitate discussions of seizure-related mortality with patients and families.

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.

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.

Does Dravet syndrome have a recognizable face?

We hypothesized that children with Dravet syndrome manifest specific facial features that can be identified by pediatric neurologists and rendered objective by standard photographic measurements. This study comprised two parts. In Part 1, photographs of children with Dravet syndrome were compiled into a booklet with patients and their siblings randomly mixed. The booklet was sent to pediatric neurologists who anonymously identified which children they thought were affected by the syndrome and which were siblings. Although pediatric neurologists generally agreed on whether children were affected or not (20/24 cases; 83%), they were frequently incorrect (12/20; 60%). In Part 2, standard photogrammetric techniques were used to provide 16 facial ratios from digital images. No significant difference in any measurement was evident between children with Dravet syndrome and unaffected siblings (P > 0.05, two-tailed t test). This study did not demonstrate a specific facial phenotype in Dravet syndrome.

Definition and natural history of Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome (LGS) is a rare epileptic encephalopathy with a peak age of onset of 3-5 years of age. Reported prevalence rates for LGS vary widely from 1-10% of all childhood epilepsies. Incidence rates are much lower. LGS is characterized by intractable, multiple, generalized seizure types and an interictal electroencephalogram showing bursts of slow spike-and-wave, paroxysmal bursts of generalized polyspikes, and a slow background. All patients have tonic seizures during sleep that may be subtle, and nearly all have treatment-resistant, lifelong epilepsy. Cognitive stagnation and behavioral problems are seen in almost all patients and lead to a life of dependency. The differential diagnosis includes other symptomatic generalized epilepsies and pseudo-Lennox syndrome. Misdiagnosis is common. Children and adults with LGS have an enormous impact on their families, and efforts to improve the quality of life for these patients are complex.

Strategies for transitioning to adult care for youth with Lennox-Gastaut syndrome and related disorders.

Transition is the process of preparing children with chronic illness and their families for the adult health care system. In patients with Lennox-Gastaut syndrome (LGS) and related disorders, the process of transition is complicated by the presence of intellectual handicap, treatment-resistant epilepsy, and behavioral issues. Patients who are not successfully transitioned to adult care may end up without specialty care, may not receive satisfactory adult services, may lack adequate follow-up and access to newer therapies, and may lack appropriate management of comorbid conditions. Several family related and clinician-related barriers can inhibit the transition process. Transition strategies that maximize each patient's ability to achieve his or her potential and optimize self-sufficiency may lead to better social outcomes. Adolescent clinics that include members of the pediatric and adult neurology teams may help ensure a smooth transition to adult care, although studies are needed to objectively establish the best model. Results are reported from a survey of 133 symposium attendees on the topic of practice characteristics and issues related to transitioning care. Results suggested a great deal of dissatisfaction about the process of transition, especially for patients with intellectual handicap. We provide suggestions for developing a transition program, including identifying a willing adult service, adapting a multidisciplinary approach, addressing legal and psychosocial issues, and celebrating rites of passage.

Juvenile myoclonic epilepsy 25 years after seizure onset: a population-based study.

OBJECTIVE: To document the long-term evolution of juvenile myoclonic epilepsy (JME) in a population-based cohort. METHODS: All patients developing JME by 16 years of age in Nova Scotia between 1977 and 1985 were contacted in 2006-2008. RESULTS: Twenty-four patients (17 women) had JME, 3.5% of all childhood-onset epilepsy. Age at first seizure was 10.4 +/- 4.3 years. We contacted 23 of 24 (96%) at a mean age of 36 +/- 4.8 years. All were initially treated with antiepileptic drugs (AEDs). At the end of a 25.8 +/- 2.4-year follow-up, 11 (48%) had discontinued treatment: 6 were seizure-free (without AEDs for 5-23 years), 3 had myoclonic seizures only (without AEDs for >18 years), and 2 continued with rare seizures. Convulsive status epilepticus occurred in 8 (36%) and 3 had intractable epilepsy. About 70% reported good satisfaction with their health, work, friendships, and social life (Likert scales). Despite 87% high school graduation, 31% were unemployed. Sixteen live with a partner, 7 alone. Nine received antidepressant medications. Ten women had > or =1 pregnancy and 4 men fathered a child. Eleven pregnancies (80%) were unplanned, outside of a stable relationship. At least 1 major unfavorable social outcome was noted in 76%. CONCLUSIONS: Our sample size is modest but the long follow-up and population-based sampling is unique. All seizure types in juvenile myoclonic epilepsy (JME) resolved in 17% and for 13%, only myoclonus persisted. Therefore, one-third of people with JME have troublesome seizures vanish and antiepileptic drug treatment is no longer needed. Depression, social isolation, unemployment, and social impulsiveness complicate the lives of many patients.

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.

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.