Cognitive and neurodevelopmental comorbidities in paediatric epilepsy.

Cognitive and behavioural comorbidities are often seen in children with epilepsy, and are more common and severe in refractory epilepsy. These comorbidities are associated with worse quality of life, increased behavioural and language problems and worse social skills, all of which adversely affect long-term psychosocial functioning. To enable early intervention and therapy, children and teens with epilepsy should be periodically screened for cognitive comorbidities. The location of the epileptic focus can, to a certain degree, predict the type(s) of comorbidity; however, the spectrum of disability is often broad, presumably because focal perturbations can cause network dysfunction. Comorbidities often result from underlying structural or functional pathology that has led to seizures. In selected cases, therapy targeting the underlying cause, such as the ketogenic diet for GLUT1 deficiency syndromes, may be remarkably effective in ameliorating both seizures and cognitive concerns. In many cases, however, cognitive impairment persists despite seizure control. In epileptic encephalopathies, frequent seizures and/or interictal epileptiform abnormalities exacerbate neurocognitive dysfunction, owing to synaptic reorganization or impaired neurogenesis, or to other effects on developing neural circuits, and prompt initiation of effective antiepileptic therapy is essential to limit cognitive comorbidities.

Development of an online tool to determine appropriateness for an epilepsy surgery evaluation.

OBJECTIVES: Despite evidence that epilepsy surgery is more effective than medical therapy, significant delays between seizure intractability and surgery exist. We aimed to develop a new Web-based methodology to assist physicians in identifying patients who might benefit from an epilepsy surgery evaluation. METHODS: The RAND/UCLA appropriateness method was used. Clinical scenarios were developed based on eligibility criteria from previously published surgical series. Thirteen national experts rated the scenarios for their appropriateness for an epilepsy surgery evaluation based on published evidence. All scenarios were rerated after a face-to-face meeting following a modified Delphi process. Appropriate scenarios were rerated for necessity to determine referral priority. RESULTS: Of the final 2646 scenarios, 20.6% (n = 544) were appropriate, 17.2% (n = 456) uncertain, and 61.5% (n = 1626) inappropriate for a surgical evaluation. Of the appropriate cases, 55.9% (n = 306) were rated as very high priority. Not attempting AED treatment was always rated as inappropriate for a referral. Trial of 2 AEDs was usually rated as appropriate unless seizure-free or not fully investigated Based on these data, a Web-based decision tool (www.epilepsycases.com) was created. CONCLUSIONS: Using the available evidence through 2008 and expert consensus, we developed a Web-based decision tool that provides a guide for determining candidacy for epilepsy surgery evaluations. The tool needs clinical validation, and will be updated and revised regularly. This rendition of the tool is most appropriate for those over age 12 years with focal epilepsy. The Rand/UCLA appropriate methodology might be considered in the development of guidelines in other areas of epilepsy care.

Social skills in children with epilepsy: how do they compare to healthy and chronic disease controls?

Studies have shown poor long-term social outcomes in adults with childhood-onset epilepsy. Our goal was to compare social skills in children with epilepsy with those of healthy and chronic disease controls. Children (8-16 years) with epilepsy (n=59) were compared with age- and gender-matched children with chronic kidney disease (n=40) and healthy controls (n=41). Parents completed the Social Skills Rating System (SSRS) questionnaire. Children with epilepsy had significantly poorer SSRS total scores when compared with healthy controls (P=0.002); however, their scores did not differ from those of children with chronic kidney disease (P=0.52). Children with epilepsy were less cooperative (P=0.02), less assertive (P=0.004), and less responsible (P=0.05) and displayed poorer self-control (P=0.005) than healthy controls. Our results suggest that having a chronic disease plays a role in the social functioning of children with epilepsy. The impact of epilepsy itself on social functioning should be further elucidated through detailed prospective assessments over time.

Are children with epilepsy at greater risk for bullying than their peers?

The primary goal of this study was to determine the prevalence of bullying in children with epilepsy compared with their healthy peers and peers with chronic disease. Children with epilepsy were compared with healthy children and a cohort of children with chronic kidney disease (CKD). The following self-report questionnaires were completed: Revised Olweus Bully/Victim, Piers-Harris Self-Concept Scale, Revised Child Manifest Anxiety Scale, Child Depression Index, and Social Skills Rating System. Children with epilepsy were more frequently victims of bullying (42%) than were healthy controls (21%) or children with CKD (18%) (P = 0.01). Epilepsy factors such as early age at seizure onset, seizure type, and refractory epilepsy were not found to be predictors of victim status. Surprisingly, poor social skills, increased problem behaviors, poor self-concept, depression, and anxiety did not correlate with bully victim status. The relatively high prevalence of bullying behaviors in these children is concerning and, from a clinical standpoint, requires greater research specifically addressing peer relationships and consideration of the implementation of anti-bullying measures and coping strategies for children with epilepsy.

Maternal depression: the cost of caring for a child with intractable epilepsy.

The aims of this study were to: (1) determine the prevalence of depression and sleep disruption in mothers of children with intractable epilepsy, and (2) assess which family factors and neurologic/behavioral characteristics of a child with epilepsy correlate with maternal depression. Mothers of children aged 2-18 years with intractable epilepsy completed a Beck Depression Inventory and Pittsburgh Sleep Questionnaire for themselves, and a Child Behavior Checklist, Attention Deficit Hyperactivity Disorder Rating Scale, and Scale of Independent Behavior-Revised for their child. Charts were reviewed for age at seizure onset, seizure frequency and type, number of failed treatments, and presence of autism. Mothers were queried regarding family type, educational level, income, and number of children in the home. Fifty-two of 80 (65%) eligible mothers returned completed questionnaires. Forty-five percent demonstrated elevated scores on the depression questionnaire, with 25% in the moderate/severely depressed range. Sleep disruption was reported in 67%. Maternal depression correlated with high attention deficit and problem behaviors in children, but not with most epilepsy-related variables, autism, adaptive delay, or family income.

Anxiety and depressive symptoms in children presenting with a first seizure.

We investigated whether children presenting with a first seizure experienced anxiety and depressive signs. Children (aged 7-17 years) with a first unprovoked afebrile seizure participated. These patients (mean age, 12 +/- 2.7 years S.D.; 14 female/8 male) completed the Revised Child Manifest Anxiety Scale (n = 22) and Children's Depression Inventory (n = 20). Scores were compared with: (1) published norms, and (2) control patients with new medical signs. Compared with the published norms, children reported greater total anxiety (P < 0.02), worry/oversensitivity (P < 0.008), and social concerns/concentration (P < 0.005). However, compared with the control patients, no difference was seen between groups. Total Children's Depression Inventory scores were higher than for published norms (P = 0.05) and control patients (P = 0.04). Children with a first seizure reported greater interpersonal problems (P < 0.01), ineffectiveness (P < 0.03), and negative self-esteem (P < 0.05) than published norms, and increased negative mood (P = 0.04), ineffectiveness (P = 0.04), anhedonia (P = 0.05), and negative self-esteem (P = 0.05) than control patients. Our results suggest that anxiety may be related to an illness or to the hospital experience itself, whereas depressive signs may be a comorbidity present at time of presentation of the first seizure. If a larger cohort substantiates these results, early screening for these signs would be of clinical importance.

Seizures in children after kidney transplantation: has the risk changed and can we predict who is at greatest risk?

Children undergoing kidney transplantation are at increased risk for symptomatic seizures with a previously reported incidence of approximately 20%. Little data exist to help predict which children may be at risk. We retrospectively reviewed all children who underwent kidney transplantation evaluation at our center between October 1993 and August 2007 and identified 41 children who had an EEG prior to transplant. Demographic data as well as the following were collected: immunosuppressive medications, developmental status, history of seizures, family history of seizures, post-transplant seizures and EEG results. EEGs were classified as normal or abnormal. Prior to transplantation, one child had a history of febrile seizures and six experienced afebrile seizures. Nine (22%) children identified had an abnormal EEG prior to transplant. In eight cases the EEG was non-epileptiform and in one case was epileptiform. Abnormal EEGs did not correlate with a family history of seizures. Delayed development was noted in seven children and was not associated with an epileptiform EEG. Following kidney transplantation, no child experienced a seizure. Our single center study suggests that current rates of seizures following kidney transplantation are lower than previously reported and that routine EEG as part of the pretransplant evaluation in these children is of limited use to predict those at risk.

Peri-ictal headache in children: prevalence and character.

Structured interviews regarding peri-ictal headaches and personal or family histories of interictal headaches were conducted on 101 children (aged 5-18 years), with generalized tonic-clonic or partial seizures. Epilepsy-specific details were collected by interviews and reviews of neurology clinic charts. Peri-ictal headaches were reported by 41% (29%, postictal only; 5%, preictal only; 7%, both). Clear migrainous features were present in 50% of preictal and 58% of postictal headaches. Most children described bilateral headaches. No demographic or epilepsy-specific correlates were identified that predicted peri-ictal headaches. Interictal headaches occurred in 24%, with 14% of children meeting criteria for migraines. However, neither interictal migraines nor a positive family history of migraines was significantly predictive of either peri-ictal headaches or migrainous peri-ictal headaches. Postictal headaches occurred reliably after most seizures in predisposed children, and interrupted activities in the majority. Whereas only half of children received abortive medications for these headaches, simple analgesics were effective in most cases. We conclude that peri-ictal headaches are common, affecting 41% of children with epilepsy. Their presence should be routinely queried, and if documented, treatment with simple analgesics appears beneficial and should be considered.

Depression, anxiety, and quality of life in siblings of children with intractable epilepsy.

Thirty-seven siblings (aged 6-18) of children with intractable epilepsy were surveyed regarding their anxiety, depression, and quality of life, by both self-report (Revised Children's Manifest Anxiety Scale, RCMAS; Children's Depression Inventory, CDI; and Peds QL) and parental report (Child Behavior Checklist, CBCL). Completed forms were returned by 37 of 58 (64%) eligible families. No sibling had a score in the clinical range on the CDI, and only 2 of 37 (6%) scored in the clinical range on the RCMAS, a proportion similar to the normative population. In contrast, 25% were rated by their parents to have elevated Internalizing Behaviors scores on the CBCL. There was a trend for PedsQL scores to be lower than the normative mean. Comorbid behavior and attention problems in the child with epilepsy and sibling CDI and RCMAS scores correlated significantly with self-reported quality of life. However, other epilepsy, child, and family variables (income, parental education, family function, maternal depression) did not correlate. We conclude that siblings of children with intractable epilepsy are functioning well overall and have a good quality of life.

Self-concept in adolescents with epilepsy: biological and social correlates.

The purposes of this study were to (1) compare self-esteem in teens with epilepsy to the normative mean, and (2) identify which neurologic/epilepsy and social/familial variables are associated with self-esteem. Thirty-seven adolescents (aged 12-18 years) attending a pediatric neurology clinic completed the Piers-Harris 2 Self-Concept Scale, Family Assessment Measure III, Child Attitude to Illness Scale, and a brief questionnaire about current seizure status (frequency, severity, and number of antiepileptic drugs). Neurology clinic charts were reviewed for seizure types, etiology, age at diagnosis, and number of failed therapies. While Total Piers-Harris t score and most subscales did not differ significantly from the normative mean, teens with epilepsy had higher scores on Behavioral Adjustment (P < 0.04) and Physical Appearance and Attributes (P < 0.03). On univariate analysis, number of current antiepileptic drugs (P < 0.05) and Attitude to Illness and Family Function scores (P < 0.02 for both) were significantly associated with self-esteem. On linear regression analysis, only the Family Function score (P < 0.02) and number of antiepileptic drugs (P < 0.05) were associated with total self-concept. We conclude that self-concept in teens with epilepsy is most strongly associated with Family Function. With the exception of current number of antiepileptic drugs used, epilepsy-specific factors are of minimal importance.

Parenting stress in mothers of children with intractable epilepsy.

OBJECTIVE: The goal of the work described here was to determine the prevalence and characteristics of maternal stress in families of children with intractable epilepsy. METHODS: Mothers of children aged 2-18 with intractable epilepsy were asked to complete the Parenting Stress Index, Scales of Independent Behavior-Revised, and Child Behavior Checklist, and were queried regarding family type, maternal education, and family income. Neurology clinic charts were reviewed for seizure variables including age at onset, number of failed therapies, and seizure frequency. The Parenting Stress Index measures stress in two broad domains [stress related to characteristics of the child (Child Domain) and stress related to characteristics of the parent (Parent Domain)] as well as a Total Stress score. RESULTS: Fifty-two of 80 (65%) eligible mothers returned completed questionnaires. Sixty-three percent scored in the clinical range for Total Stress, 75% for the Child Domain, but only 29% for the Parent Domain. Mothers scored more adversely on the Isolation, Health, Role Restriction, and Spouse subscales of the Parent Domain, but more favorably on the Attachment subscale. A moderate to high correlation was noted between behavior problems in the child and higher Total Stress scores, but no significant correlations were found between other seizure or demographic variables. CONCLUSION: Intractable childhood epilepsy is associated with markedly increased maternal parenting stress. Increased stress is due predominantly to child factors. Mothers would strongly benefit from added support to alleviate the constant caregiving demands.

Do children with benign rolandic epilepsy have a higher prevalence of migraine than those with other partial epilepsies or nonepilepsy controls?

PURPOSE: Prior studies have given conflicting data concerning the association of benign rolandic epilepsy of childhood (BREC) and migraine but were limited by lack of sensitive, diagnostic criteria for childhood migraine. By using revised International Headache Society (IHS-R) criteria, we compared the prevalence of migraine in children with BREC with that of those (a) with cryptogenic/symptomatic partial epilepsy and (b) without epilepsy. METHODS: Three cohorts of children, gender and age matched (within 1 year) were identified: (a) BREC, (b) cryptogenic/symptomatic partial epilepsy, and (c) no history of seizures. Parents were queried in a standardized interview about migraine and migraine equivalents in their child, and in either biologic parent. Migraine was defined by using the IHS-R (for children) and IHS criteria (for parents). Children with headache were divided into definite (meeting IHS-R criteria), probable (recurrent, throbbing headaches with nausea, vomiting, photophobia or phonophobia, not meeting IHS-R criteria), possible (recurrent headaches with throbbing character or associated nausea/vomiting), or nonmigraine groups. chi(2) analysis was used to determine whether the cohort with BREC had a higher prevalence of definite, definite or probable, or definite, probable, or possible migraines or migraine equivalents than the other two cohorts. RESULTS: Each cohort consisted of 53 children (mean age, 9.8-9.9 years, M/F ratio, 35:18). Those with BREC had higher rates of definite and probable (p = 0.05), of definite, probable, and possible migraine (p = 0.05), and of migraine equivalents excluding motion sickness (p < 0.005) than did those without seizures; however, they did not differ significantly from the cryptogenic/symptomatic partial epilepsy cohort. CONCLUSIONS: Partial epilepsy, regardless of etiology, is associated with higher rates of migraine in children. The pathophysiologic link between epilepsy and migraine is unknown.