Outcome of childhood-onset epilepsy from adolescence to adulthood: Transition issues.

This is the second of three papers that summarize the second symposium on Transition in Epilepsies held in Paris in June 2016. This paper addresses the outcome for some particularly challenging childhood-onset epileptic disorders with the goal of recommending the best approach to transition. We have grouped these disorders in five categories with a few examples for each. The first group includes disorders presenting in childhood that may have late- or adult-onset epilepsy (metabolic and mitochondrial disorders). The second group includes disorders with changing problems in adulthood (tuberous sclerosis complex, Rett syndrome, Dravet syndrome, and autism). A third group includes epilepsies that change with age (Childhood Absence Epilepsy, Juvenile Myoclonic Epilepsy, West Syndrome, and Lennox-Gastaut syndrome). A fourth group consists of epilepsies that vary in symptoms and severity depending on the age of onset (autoimmune encephalitis, Rasmussen's syndrome). A fifth group has epilepsy from structural causes that are less likely to evolve in adulthood. Finally we have included a discussion about the risk of later adulthood cerebrovascular disease and dementia following childhood-onset epilepsy. A detailed knowledge of each of these disorders should assist the process of transition to be certain that attention is paid to the most important age-related symptoms and concerns.

Inconsistency between prospectively and retrospectively reported febrile seizures.

This study compared the incidence of febrile seizures (FS) reported prospectively up to 5 years of age, with the prevalence of FS by parental recall in the same cohort using the same questionnaire at 12 years of age. Both prospective and retrospective data were available for 807 children (389 males, 418 females). The number of children reported to have experienced FS in the prospective study was 57, and in the retrospective study was 45, yielding a cumulative incidence of 7.1 and 5.6% respectively. In the retrospective study there was an under-reporting of 19 children, over-reporting of eight children, and one child misreported by age at onset. Overall sensitivity of the retrospective approach was 65% and specificity was 99%. Positive predictive value was 82% and negative predictive value was 97%. Retrospective data underestimate the frequency of FS with high specificity but low sensitivity. Recall data suggest that some children with FS were not reported in the prospective data. These biases should be considered when evaluating the value of FS as a predictor of future health effects.

Paroxysmal eyelid movements: a confusing feature of generalized photosensitive epilepsy.

BACKGROUND: Persistent, frequent, nonepileptic paroxysmal eyelid movements were observed in 19 children and adults with well-controlled generalized epilepsy. METHODS: Patients were identified from five epilepsy centers. RESULTS: Seventeen patients were female and two male. All had generalized photosensitive epilepsy requiring antiepileptic drugs (AEDs). In two children, paroxysmal eyelid movements began 2 to 4 years before their epilepsy was noted; in the remainder, it was noted when epilepsy was first diagnosed. Age at last follow-up was 8 to 38 years (average 21 years) with average follow-up of 9 years. All patients showed photosensitive generalized spike-wave discharges on EEG. Paroxysmal eyelid movements were a source of diagnostic confusion, but direct examination and video during EEG recording distinguished the attacks from absence seizures. In all cases, the epilepsy is completely or nearly completely controlled with AEDs, but the paroxysmal eyelid movements have not resolved with age. In 12 cases, there was a family history of the eyelid disorder without epilepsy. Videos of patients and an affected parent are available on the Neurology Web site. CONCLUSION: There is an association between paroxysmal eyelid movements and photosensitive generalized epilepsy, creating diagnostic confusion.

Botulinum toxin A as a treatment for excessive drooling in children.

Drooling is problematic for some neurologically impaired children. Botulinum toxin A injection to salivary glands has effectively reduced drooling in adults but has only recently been used to treat children. This was a preliminary study to determine the efficacy and safety of botulinum toxin in children. Children identified as having severe daily drooling were enrolled. The preinjection assessment included measurement of the amount and frequency of drool. Each parotid gland was injected with 5 U of botulinum toxin A. Follow-up was for a minimum of 16 weeks. Nine children were enrolled, 4-17 years of age. All children had moderate or severe mental retardation. At week 4, all patients had a reduced drooling frequency and eight of nine patients had a reduction in the weight of saliva. Overall, five of nine parents (55%) deemed the treatment successful. This preliminary study demonstrates that botulinum toxin A is a relatively effective treatment for some children with significant drooling without serious side effects.

Duchenne muscular dystrophy--parental perceptions.

Quality of life and availability of services are important for boys with Duchenne muscular dystrophy (DMD) and their families. Families attending our neuromuscular clinic completed a questionnaire on parental perception regarding the importance of services, health issues, and quality of life issues both "now" and "in the future." Eighty-nine percent of the families (31/35) completed questionnaires. Services and health issues related to prolonging ambulation were most important, especially for the parents of younger boys. Mental health issues such as social isolation, anger, and depression were very important, particularly for the families of older boys and were anticipated to be more important in the future. Pediatricians should be aware of both the immediate needs of families to meet the physical and emotional challenges of DMD and the increasing requirement to address the social needs of these patients and their families as the boys become older.

Parents of children with epilepsy are optimistic for their children's health, but relatively pessimistic when compared with other parents.

We examined parents' perceived risk of their children encountering 10 general health conditions and 10 epilepsy-specific health problems using a standard optimistic bias question with standard responses. "Compared to other children of similar age, my child's chance of getting [problem, e.g., kidney disease] in the future is" (on a 7-point response scale) "much below average em leader average em leader much above average." "Pessimistic" parents were defined as those whose mean answers exceeded average risk. Parents demonstrated an optimistic bias for most health risks. For all the general health risks, the parents of children with epilepsy showed less optimistic bias (or pessimism) (P=0.001). Parents of children with epilepsy were much more likely to be "pessimistic" about future health risks (odds ratio 3.0, 95% CI: 1.1, 8.4) but showed an optimistic bias for the epilepsy-specific health risks. Parents of children with epilepsy appear to judge their children as more vulnerable to additional health problems when compared with parents of healthy children.

Treatment of febrile seizures: the influence of treatment efficacy and side-effect profile on value to parents.

OBJECTIVES: We examined parents' perception of the value of treatments designed to reduce the risk of febrile seizure recurrence. STUDY DESIGN: The families of 42 children with febrile seizures were recruited after pediatric or neuropediatric consultation. A mail questionnaire addressed the family's willingness to pay for a hypothetical treatment for febrile seizures with risk reductions for future febrile seizures of 25%, 50%, 75%, and 100%. The hypothetical clinical scenario was then modified to include the side- effect profiles of either daily phenobarbital or valproic acid, or intermittent diazepam prophylaxis. Covariates included the nature of the child's febrile seizure(s), parents' familiarity with febrile seizures, experiences at the time of febrile seizures or with medication side effects, education and income, and mastery and trait anxiety. RESULTS: Thirty-eight parents, representing 22 of 42 families, completed questionnaires. There was a dramatic inflection in parents' willingness to pay for 100% risk reduction as opposed to 75% or lower risk reductions. Introduction of side effects dramatically reduced the value attached to each level of treatment benefit. Nevertheless, a few parents (3/38) would pay "as much as it takes" to be rid of their child's recurrence risk. CONCLUSIONS: Given the range of value assigned to prophylactic medication for febrile seizures, management strategies for children with febrile seizures must be responsive to the needs and values of individual families.

Irritability in Krabbe's disease: dramatic response to low-dose morphine.

Krabbe's disease is characterized by normal neonatal development with subsequent regression and profound, medically intractable irritability. Two female infants presented at 5 months of age with increasing irritability, abnormal motor control, and developmental regression. Investigations confirmed the diagnosis of Krabbe's disease. Maximal treatment of gastroesophageal reflux and nitrazepam 0.1 mg/kg by mouth three times daily were unsuccessful in controlling irritability. Morphine was initiated and titrated to 0.06 mg/kg by mouth every 6 hours in Patient 1 and 0.1 mg/kg by mouth every 8 hours in Patient 2, resulting in remarkably successful control of irritability. The diagnosis of Krabbe's disease is devastating for families and is compounded by the marked irritability. Management is difficult, but in these two infants, irritability was successfully controlled with low-dose morphine.

Population study of benign rolandic epilepsy: is treatment needed?

Forty-three of 79 children (54%) with benign rolandic epilepsy from a regional population were treated with antiepileptic drugs (AED); 36 (46%) were not. Physician advice was a major determinant of treatment choice. AED significantly reduced generalized seizures (p = 0.001) but did not reduce partial seizures. After 4 to 14 years and >900 seizures, all patients were in remission without medication or injury. Physicians may confidently offer a no-AED treatment strategy.

Treatment of children with "ordinary" epilepsy.

Many children with epilepsy have a relatively benign clinical course with eventual remission of their seizures and no further need for medication. It is not easy to be sure who these children are at the time of diagnosis, but they do not have catastrophic epilepsy. Epilepsy is best defined as two unprovoked seizures. Not all of these children require treatment and treatment is motivated by fear of brain damage, injury, death, kindling of additional seizures, and social consequences. None of these fears provides an absolute indication for treatment. The decision to start medication should be considered on an individual basis. The choice of a first AED is arbitrary with most AEDs having equal efficacy. Follow-up schedules have not been well studied. However, there is fairly convincing evidence that routine blood and urine screening for toxicity is of no benefit, if the child is asymptomatic. Serum drug levels are of little clear benefit. Once the child has been seizure-free for 6 months to 12 months, it is reasonable to consider stopping medication. Only rarely does seizure control fail to return if there are recurrences without medication.

Children with febrile seizures do not consume excess health care resources.

BACKGROUND: Febrile seizures are benign but so terrifying for parents that they may subsequently view their affected children as "vulnerable". Children viewed as vulnerable may be brought to medical attention more frequently. We examined subsequent hospitalizations and physician visits during a 6- to 7 1/2-year period for a group of children who had participated in a case-control study of initial febrile seizures. METHODS: Individual data from a regional cohort of 75 children with a first febrile seizure and 150 febrile and 150 afebrile controls were linked to 2 comprehensive provincial health services databases-a hospital admissions/ separations database and a physician services database. RESULTS: Linkage was achieved for 98% of the study cohort, with heath care utilization data for 6 to 7 1/2 years available for 96%. Children with febrile seizures had nearly identical rates of subsequent hospitalization compared with age-matched controls (chi2 test, P = .88). An excess of day-surgery visits for primarily otolaryngologic procedures was seen for the febrile seizure patients 0 to 12 months after their initial febrile seizure (chi2 test, P < .001). During the next 6 to 7 1/2 years, the febrile seizure patients had nearly identical rates of physician visits (chi2 test, P = .15); however, they had more visits to otolaryngologists in the first 3 to 9 months after the febrile seizure (chi2 test, P < .001), but fewer visits to pediatricians during the next 1 to 4 years (chi2 test, P < .001). CONCLUSIONS: Children with febrile seizures have nearly identical rates of hospital and physician services utilization compared with controls. This supports the hypothesis that febrile seizures are benign, and that parents recover from their initial anxiety and do not consider their children vulnerable to additional illness in the years that follow.

Double-blind methylphenidate trials: practical, useful, and highly endorsed by families.

OBJECTIVE: To evaluate a 3-week, randomized, double-blind, methylphenidate placebo-controlled trial (MPT) in routine practice for children with attention-deficit disorder. PATIENTS AND METHODS: School-aged children with attention-deficit/hyperactivity disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) who enrolled an "N of 1" trial at a pediatric tertiary care center were eligible. Families (n = 50) with a child eligible for the MPT were given 3 bottles of identical capsules. The capsules contained, in random order: placebo of the prescribed dose of methylphenidate (Ritalin) hydrochloride (0.3 mg/kg or 0.6 mg/kg). Families gave the child 1 capsule at 8 AM and 1 capsule at noon. The family, teacher, and physician were blinded for the order of medication. Conners questionnaires (Conners Parent Questionnaire and Conners Teacher Questionnaire) and written comments were completed by parents and teachers at baseline and at the end of each week. Once MPT results were known and following discussion with the physician, families decided whether to continue methylphenidate therapy. Families were interviewed by telephone 14 to 21 months after the MPT. RESULTS: Forty-three (86%) of the 50 eligible children (mean age, 129 months) were contacted. No family found the MPT difficult, but 6 trials were incomplete, usually because of side effects. All families used the MPT to decide if methylphenidate was the correct treatment choice for their child and 68% (34 of 50 families) used the results exclusively. The remaining 16 families believed the MPT was helpful. Overall, 31 (72%) of the 43 children had a good response to methylphenidate treatment--20 (47%) continued to use it for longer than 12 months and 8 (26%) for 2 to 12 months; 3 responders chose not to use it after the MPT. Nine of the 43 families chose not to use methylphenidate treatment; however, all indicated that participating in the MPT helped them to make that decision. In follow-up interviews, the same proportion of methylphenidate users and nonusers reported improvement in many areas of function including significantly less time spent doing homework. Users reported reduced aggression (P<.001) and fewer discipline problems (P<.01) compared with nonusers. CONCLUSIONS: An "N of 1" MPT was easily performed and permitted families to decide whether to use methylphenidate for long-term treatment of attention-deficit disorder or attention-deficit/hyperactivity disorder. Regardless of methylphenidate use or lack of use, the condition of all of these children was improved at follow-up.

Topiramate in intractable childhood onset epilepsy--a cautionary note.

OBJECTIVES: To study the effectiveness and safety of topiramate in clinical practice, for a group of patients with childhood onset epilepsy. METHODS: All patients treated with topiramate at the three study centers between November 1995 and December 31, 1997 were analyzed retrospectively, using a standardized study protocol. Data were gathered on demographic features, seizures response and medication related adverse events. RESULTS: Eighty-seven patients were treated with topiramate. Over 90% seizure reduction was achieved in 8 (9%) patients, 50%-90% in 21 (24%), < 50% in 54 (62%) patients. Four patients (5%) had a deterioration in seizure control. Adverse events required topiramate discontinuation in 36 (41%). Of these 27 (31%) complained of unacceptable cognitive dulling. The rate of dose escalation and final dose in mg/kg were similar in those who remained on topiramate and those who were intolerant because of cognitive side effects. CONCLUSIONS: Although topiramate resulted in > 50% seizure reduction in 29 (33%) of this group of patients with difficult epilepsy, its usefulness was limited by a high incidence of adverse effects. Adverse events prevented ongoing therapy for 36 (41%) and cognitive dulling resulted in topiramate discontinuation by 27 (31%) of the group.

The cognitive and behavioural effects of clobazam and standard monotherapy are comparable. Canadian Study Group for Childhood Epilepsy.

PURPOSE: To compare the cognitive and behavioural effects of clobazam versus standard monotherapy in the treatment of childhood epilepsy. METHODS: A randomized, double-blind, prospective design was carried out at three Canadian pediatric epilepsy centres. This study was part of a larger multi-centre study on the efficacy of clobazam. Children with newly diagnosed epilepsy were assigned randomly to receive clobazam or carbamazepine. Children who had failed previous treatment with carbamazepine were assigned randomly to clobazam or phenytoin. Children who had failed on any other antiepileptic drug were assigned randomly to receive clobazam or carbamazepine. In a subset of patients neuropsychological assessments were carried out at 6 weeks and 12 months after initiation of medication. Intelligence, memory, attention, psychomotor speed, and impulsivity were assessed. RESULTS: There were no differences between the clobazam and standard monotherapy groups on any of the neuropsychological measures obtained at 6 weeks or 12 months. There was no evidence for a deterioration in performance for those children who remained on clobazam for the entire 12-month study period. CONCLUSION: The cognitive and behavioural effects of clobazam appear to be similar to those of standard monotherapy.

A multicenter study of the efficacy of the ketogenic diet.

OBJECTIVE: To determine the efficacy of the ketogenic diet in multiple centers. DESIGN: A prospective study of the change in frequency of seizures in 51 children with intractable seizures who were treated with the ketogenic diet. SETTING: Patients were enrolled from the clinical practices of 7 sites. The diet was initiated in-hospital and the patients were followed up for at least 6 months. PATIENTS: Fifty-one children, aged 1 to 8 years, with more than 10 seizures per week, whose electroencephalogram showed generalized epileptiform abnormalities or multifocal spikes, and who had failed results when taking at least 2 appropriate anti-epileptic drugs. INTERVENTION: The children were hospitalized, fasted, and a 4:1 ketogenic diet was initiated and maintained. MAIN OUTCOME MEASURES: Frequency of seizures was documented from parental calendars and efficacy was compared with prediet baseline after 3, 6, and 12 months. The children were categorized as free of seizures, greater than 90% reduction, 50% to 90% reduction, or lower than 50% reduction in frequency of seizures. RESULTS: Eighty-eight percent of all children initiating the diet remained on it at 3 months, 69% remained on it at 6 months, and 47% remained on it at 1 year. Three months after initiating the diet, frequency of seizures was decreased to greater than 50% in 54%. At 6 months, 28 (55%) of the 51 initiating the diet had at least a 50% decrease from baseline, and at 1 year, 40% of those starting the diet had a greater than 50% decrease in seizures. Five patients (10%) were free of seizures at 1 year. Age, sex, principal seizure type, and electroencephalogram were not statistically related to outcome. CONCLUSION: The ketogenic diet is effective in substantially decreasing difficult-to-control seizures and can successfully be administered in a wide variety of settings.

Outcome of neonatal stroke in full-term infants without significant birth asphyxia.

UNLABELLED: Seven children with neonatal stroke were identified and six were followed for 13 months to 5 years (mean 28 months). Gestational age ranged between 39 and 42 weeks and none had hypoxic ischaemic encephalopathy. Focal clonic seizures were the presenting feature in six, and one presented with apnoea. The age of the first seizure ranged between 8 and 48 h (mean 26). The total number of seizures ranged between 3 and 10 (mean 5), and all seizures resolved by day 3 in all cases. CT scan showed an ischaemic infarct in six cases, and one child had a haemorrhagic infarct in the right anterior cerebral artery distribution. Phenobarbital was maintained for 3 weeks to 6 months (mean 11 weeks). None had recurrent seizures beyond the 3rd day of life and all were developing normally with no significant focal neurological deficits on follow up assessment. CONCLUSIONS: Full-term infants with neonatal stroke unrelated to significant birth asphyxia have a favourable neurological outcome. Seizures appear to be restricted to the first 3 days of life. We recommend short-term treatment with anticonvulsants.

Peer relationship problems in children with Tourette's disorder or diabetes mellitus.

Peer relationships, social skills, self-esteem, parental psychopathology, and family functioning of children with Tourette's disorder and a chronic disease control group of children with diabetes mellitus were compared. Children with Tourette's disorder had poorer peer relationships than their classmates and were more likely to have extreme scores reflecting increased risk for peer relationship problems than children with diabetes mellitus, but did not report self-esteem problems or social skills deficits. Measures of peer relationships were not related to severity or duration of tics. Children with Tourette's disorder and Attention Deficit Hyperactivity Disorder were at increased risk for poor peer relationships. The psychosocial problems of children with Tourette's disorder do not appear to be the generic result of having a chronic disease.

Children with familial cryptogenic epilepsy have a favorable seizure prognosis.

We examined the prognosis for children with epilepsy not conforming to a genetic syndrome, who also had close relatives with epilepsy. Probands, with no identified cause for epilepsy except a first-degree relative with epilepsy, were identified from a population-based cohort of 504 children in Nova Scotia, with onset of seizures between 1977 and 1985. The primary outcome measure was seizure remission after an average of 15 years follow-up for probands (n = 27) and 26 years for their affected relatives (n = 32). Of probands, 92% were seizure free for 3 or more years at the end of follow-up, compared with 76% of relatives. When seizures began before age 12 years, 96% of probands and 94% of affected relatives were seizure free at the end of follow-up. There was little concordance for the details of the clinical course between probands and affected family members. This high level of remission was considerably better than for similar patients from the original Nova Scotian cohort (P < .02). We conclude that children with epilepsy not conforming to a well-defined genetic syndrome, but with an affected first-degree relative, have a remarkably good prognosis.