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.

Vitamin E supplementation in beef finishing diets containing 35% wet distillers grains with solubles: feedlot performance and carcass characteristics.

Supplementation of vitamin E has indications for improving cattle health, performance, and retail characteristics when included in grain-based diets. This experiment was conducted to determine performance and carcass characteristics of steers fed diets containing wet distillers grains with solubles (WDGS) and supplemented with vitamin E. Steers of mixed Bos indicus and Bos taurus breeding (n = 199; BW = 363 ± 32 kg) were blocked by BW and assigned to 1 of 4 supplemental vitamin E (VITE) treatments [0 (control), 125, 250, and 500 IU·steer(-1)·d(-1)], which were fed for the last 97 d of the feeding period. Two blocks were on feed 129 d, and 3 blocks were fed for 150 d. Steers were fed a dry-rolled corn-based finishing diet with 35% WDGS (DM basis). Individual BW were measured initially, the initial day of vitamin E supplementation, and the day of slaughter. Carcass weights were collected at slaughter, and carcass data were collected after a 36-h chill. Body weight and ADG were not affected by VITE (P ≥ 0.34). There was a tendency for a linear (P = 0.08) increase in carcass-adjusted BW with increasing VITE. Use of carcass-adjusted final BW resulted in a linear increase (P = 0.04) in ADG with increasing VITE. Pre-vitamin E and vitamin E feeding period DMI were not affected (P ≥ 0.24) by VITE, but there was a tendency (P = 0.08) for a linear increase in overall DMI with increasing VITE. No difference (P ≥ 0.29) occurred in G:F measures using BW gains, but G:F using carcass-adjusted BW gains resulted in a trend (P = 0.11) for G:F to increase linearly with increasing VITE. Hot carcass weights tended (P = 0.08) to increase linearly with increasing dietary vitamin E. Vitamin E supplementation resulted in no effects (P ≥ 0.13) on measured carcass characteristics. Calculated yield grades (YG) were also not affected (P ≥ 0.37). However, the distribution of calculated YG resulted in a quadratic effect (P = 0.02) for YG 3 with the control and 500 VITE being greater than the 2 intermediate amounts. However, the percentage of carcasses grading YG 3 or less were not affected by vitamin E supplementation (P = 0.64). No differences were observed in the distribution of quality grades based on marbling scores (P ≥ 0.57). Data from this study suggest that vitamin E supplemented above basal requirements during the last 97 d of the feeding period in finishing diets containing 35% WDGS results in slight to no effect on animal performance or carcass characteristics.

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.

Practice parameter: treatment of the child with a first unprovoked seizure: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.

The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence regarding risks and benefits. This parameter reviews published literature relevant to the decision to begin treatment after a child or adolescent experiences a first unprovoked seizure and presents evidence-based practice recommendations. Reasons why treatment may be considered are discussed. Evidence is reviewed concerning risk of recurrence as well as effect of treatment on prevention of recurrence and development of chronic epilepsy. Studies of side effects of anticonvulsants commonly used to treat seizures in children are also reviewed. Relevant articles are classified according to the Quality Standards Subcommittee classification scheme. Treatment after a first unprovoked seizure appears to decrease the risk of a second seizure, but there are few data from studies involving only children. There appears to be no benefit of treatment with regard to the prognosis for long-term seizure remission. Antiepileptic drugs (AED) carry risks of side effects that are particularly important in children. The decision as to whether or not to treat children and adolescents who have experienced a first unprovoked seizure must be based on a risk-benefit assessment that weighs the risk of having another seizure against the risk of chronic AED therapy. The decision should be individualized and take into account both medical issues and patient and family preference.

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.

Acute pancreatitis causing death in a child on the ketogenic diet.

The ketogenic diet has demonstrated good efficacy in children with pharmacologically resistant seizures. Relatively few serious complications have been reported in the more than 70 years in which the diet has been used. We report a child who developed acute pancreatitis and died. A 9-year-old girl had a seizure disorder with associated developmental delay owing to glucose transport protein deficiency. The ketogenic diet with medium chain triglyceride oil had been initiated shortly after diagnosis in infancy. She was not on anticonvulsants. She presented in coma with decreased respiratory effort and shock, requiring resuscitation. Investigations were consistent with pancreatitis. Despite fluid resuscitation and inotropic support, she had prolonged hypotension and acidosis. She subsequently had a cardiac arrest and died. A postmortem examination confirmed hemorrhagic pancreatitis. Hypertriglyceridemia is a risk factor for developing acute pancreatitis. The high fat content of the ketogenic diet often causes hyperlipidemia. The outcome for this patient raises concern regarding a potential consequence of the ketogenic diet.

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.

Prognostic significance of failure of the initial antiepileptic drug in children with absence epilepsy.

PURPOSE: In children with childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE), to determine the impact of failure of initial antiepileptic drug (AED) for lack of efficacy in eventual seizure control and long-term remission of epilepsy. METHODS: Centralized EEG records for the province of Nova Scotia allowed identification of all children seen with CAE or JAE between 1977 and 1985. Information regarding success or failure of initial AED in fully controlling seizures and long-term seizure control and remission of epilepsy was collected by patient questionnaire and chart review. RESULTS: Eighty-six of 92 eligible patients were followed up (75 CAE, 11 JAE). Initial AED treatment was successful in 52 (60%) of 86. Success tended to be greater for valproate (VPA) than for other AEDs (p = 0.07), and lower if generalized tonic-clonic or myoclonic seizures coexisted (p < 0.004 and p < 0.03). Terminal remission was more likely if the initial AED was successful than if it had failed (69% vs. 41%; p < 0.02). Compared with those in whom the initial AED was successful, subjects whose initial AED had failed were more likely to progress to juvenile myoclonic epilepsy (JME) at last follow-up (32% vs. 10%; p < 0.02) and to develop intractable epilepsy (17% vs. 2%; p < 0.04). CONCLUSIONS: Initial AED was successful in 60% of children with AE. If the first AED failed, the outcome was less favorable, with a lower rate of terminal remission and a higher rate of progression to JME and intractable epilepsy.

Impact of pediatric epilepsy on the family: a new scale for clinical and research use.

PURPOSE: There is no brief, global instrument available that specifically measures the psychosocial impact of pediatric epilepsy on the family. An 11-item scale was created for parents' use to evaluate the influence of epilepsy on the major aspects of their family and child's life. This will be a helpful tool both in the clinical setting and as an outcome measure for research studies. METHODS: Mothers rated their child's quality of life on a visual analogue scale (1-6) and completed the Impact of Pediatric Epilepsy Scale (IPES), which assesses the impact on academic achievement, participation in activities, health, relationships with family and with peers and siblings, social activities, self-esteem, and the caregiver's hopes for their child's future adapted from the scale developed by Jacoby. External validation was determined by comparison of the IPES with physicians' reports of the characteristics of the child's epilepsy and neurological limitations and parents' ratings on the Family Environment Scale or Parenting Stress Index. In addition, each school-aged child completed the Piers-Harris Children's Self-Concept Scale, Brother-Sister Questionnaire, and Loneliness Scale. Teachers of children completed the Academic Performance Rating Scale. Seven days later, retest reliability of the IPES was evaluated. RESULTS: Ninety-seven mothers of children aged 2-16 years completed the IPES and the appropriate family and age-related questionnaires. Internal validation on the IPES yielded a Cronbach's a for the scale of 0.92. A significant Pearson's correlation indicated that total scores were consistent over time (r = 0.81). Spearman's correlations for the individual items were also significant, ranging from 0.48 to 0.78. Significant Spearman's correlations also indicated that quality of life was negatively related to impact on each of the 11 items of psychosocial function. Children with IPES scores above the median differed in some psychosocial aspects from those who scored below. Their parents were more stressed, their siblings were more respectful, they had lower self-esteem, and they experienced more emotional problems. Total impact was also significantly related to seizure frequency, total number of medications taken, number of visits to a physician in the previous year, and number of nights spent in hospital for neurological reasons. CONCLUSIONS: The IPES is an accurate, acceptable, and quick measurement tool that reflects the way in which childhood epilepsy has an impact on the child and on family life. It may be helpful in routine clinical care and may be useful in the research setting to find ways to improve the lives of children with epilepsy.

How often does routine pediatric EEG have an important unexpected result?

BACKGROUND: Electroencephalogram recordings are requested for the assessment of many childhood disorders. To assess the utility of the EEG in children, we studied how often routine EEG results can be correctly predicted from the EEG requisition. METHOD: Five hundred consecutive initial EEG requests from the IWK Grace Health Centre from two time epochs were examined. All EEGs were 16 channel (10-20 electrode system). Based only on the requisition (patient demographics, referring physician, and reason for EEG), we coded our prediction of the result and then the actual result. When results were discordant from prediction, a judgment was made about the potential importance of the result. RESULTS: Overall, EEG results were correctly predicted in 81%. Prediction for all nonepilepsy reasons was accurate in 91% (n=320) and 96% for paroxysmal nonepileptic events (n=158) but only 59% for epileptic disorders (n=141) (p<0.0001). Neurologists ordered 45% of EEGs, pediatricians 32%, and GP's 17%. Predictions were least accurate for neurologists' requests (p<0.006) however, neurologists were more likely to request EEG for epileptic disorders (p<0.0001). Age of the child and urban versus rural address did not affect the accuracy of prediction. CONCLUSION: Results of routine pediatric EEG for most nonepilepsy reasons appear highly predictable and therefore, possibly of little value to an experienced clinician. When requested for epilepsy, this "ancient" test remains full of surprises.

Epilepsy can be diagnosed when the first two seizures occur on the same day.

PURPOSE: Experts have suggested that when the first two (or more) unprovoked seizures occur on the same day, they should be considered as a single event and the diagnosis of epilepsy await a further seizure. We have studied the subsequent clinical course of children with their first two seizures on the same day ("same day" group) compared with children with their first two seizures separated by more than one day ("different day" group). METHOD: The Nova Scotia childhood epilepsy database documented all newly diagnosed children with epilepsy from 1977 to 1985 with follow-up in 1990 and 1991. Epilepsy was defined as two or more unprovoked seizures regardless of the interval between seizures provided that consciousness fully returned between seizures. All patients had their first seizure between the ages of 1 month and 16 years. Seizure types were restricted to partial, generalized tonic-clonic, and partial with secondary generalization. RESULTS: Of the 490 children with partial or generalized tonic-clonic seizures and follow-up of more than 2 years, 70 had their first two or more seizures on the same day and 420 had their first two seizures on different days. Eighty percent (56 of 70) of the "same day" group subsequently had one or more further seizures with (n = 14) or without (n = 42) medication; 80.9% (340 of 420) of the "different day" group had one or more further seizures with (n = 115) or without (n = 225) medication. Seizure types were nearly identical. Cause was the same (except for fewer idiopathic "genetic" cases in the "same day" group: 1 of 70 vs. 42 of 420; p = 0.02). Rates of mental handicap and previous febrile seizures were the same. Children in the "same day" group were younger on average (60 vs. 84 months; p = 0.001) and were somewhat more likely to have neurological impairment. Outcome after 7 years average follow-up was the same: 58% of the "same day" group and 56% of the "different day" group were in remission. CONCLUSION: If two or more unprovoked seizures (with normal consciousness between) occur on the same day, the child appears to have epilepsy and will have a clinical course identical to that of the child with a longer time interval between the first two seizures.

Practice parameter: evaluating a first nonfebrile seizure in children: report of the quality standards subcommittee of the American Academy of Neurology, The Child Neurology Society, and The American Epilepsy Society.

OBJECTIVE: The Quality Standards Subcommittee of the American Academy of Neurology develops practice parameters as strategies for patient management based on analysis of evidence. For this practice parameter, the authors reviewed available evidence on evaluation of the first nonfebrile seizure in children in order to make practice recommendations based on this available evidence. METHODS: Multiple searches revealed relevant literature and each article was reviewed, abstracted, and classified. Recommendations were based on a three-tiered scheme of classification of the evidence. RESULTS: Routine EEG as part of the diagnostic evaluation was recommended; other studies such as laboratory evaluations and neuroimaging studies were recommended as based on specific clinical circumstances. CONCLUSIONS: Further studies are needed using large, well-characterized samples and standardized data collection instruments. Collection of data regarding appropriate timing of evaluations would be important.

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.