Provider Practices of Phenobarbital Discontinuation in Neonatal Seizures.

Neonatal seizures are treated with phenobarbital and prolonged treatment does not prevent postneonatal epilepsy. The authors documented factors influencing phenobarbital use and determined whether published data changed practice. A total of 83 neonates with symptomatic seizures, clinical or electrographic, were evaluated for treatment, incidence of postneonatal epilepsy, and associated factors. Median phenobarbital treatment was 81 days. Nineteen children (23%) developed postneonatal epilepsy. Longer duration of seizures and an infectious etiology were associated with postneonatal epilepsy suggesting no impact on duration of phenobarbital treatment. Treatment duration was associated with duration of seizures and use of a second antiseizure medication. This study supports early discontinuation of phenobarbital and suggests providers utilize factors such as use of a second antiseizure medication and time to seizure control to determine phenobarbital duration, despite prior studies suggesting no impact of treatment length.

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.

Stiripentol in Dravet syndrome: results of a retrospective U.S. study.

PURPOSE: To review the efficacy and tolerability of stiripentol in the treatment of U.S. children with Dravet syndrome. METHODS: U.S. clinicians who had prescribed stiripentol for two or more children with Dravet syndrome between March 2005 and 2012 were contacted to request participation in this retrospective study. Data collected included overall seizure frequency, frequency of prolonged seizures, and use of rescue medications and emergency room (ER)/hospital visits in the year preceding stiripentol initiation, and with stiripentol therapy. We separately assessed efficacy in the following treatment groups: group A, stiripentol without clobazam or valproate; group B, stiripentol with clobazam but without valproate; group C, stiripentol with valproate but without clobazam; and group D, stiripentol with clobazam and valproate. In addition, adverse effects were recorded. KEY FINDINGS: Thirteen of 16 clinicians contacted for study participated and provided data on 82 children. Stiripentol was initiated a median of 6.0 years after seizure onset and 1.2 years after diagnosis of Dravet syndrome. Compared to baseline, overall seizure frequency was reduced in 2/6 in group A, 28/35 in group B, 8/14 in group C, and 30/48 in group D. All children with prolonged seizure frequency greater than quarterly during the baseline period experienced a reduction in this frequency on the various treatment arms with stiripentol. Similarly, 2/4 patients in group A, 25/25 in group B, 5/10 in group C, and 26/33 in group D experienced reduction in frequency of rescue medication use and 1/1 in group A, 12/12 in group B, 3/5 in group C, and 18/19 in group D had reduction in frequency of ER/hospital visits. Adverse effects were reported in 38, most commonly sedation and reduced appetite. Four patients (5%) discontinued stiripentol for adverse effects and two (2%) for lack of efficacy. SIGNIFICANCE: Stiripentol is an effective and well-tolerated therapy that markedly reduced frequency of prolonged seizures in Dravet syndrome.

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 outcomes after temporal or extratemporal epilepsy surgery: a systematic review.

PURPOSE: The objective of this study was to systematically review the literature to assess social outcomes after epilepsy surgery. METHODS: A systematic literature search was conducted as part of a larger project on the development of an appropriateness and necessity rating tool to identify patients with focal epilepsy that may benefit from an epilepsy surgery evaluation. Studies were included if they reported postsurgical data on social outcomes (employment, driving, social relationships, marriage, education, financial status, behavior, and social interactions) and had a follow-up period of at least 24 months. Our search strategy yielded 5,061 studies. Sixty-five of these studies addressed social outcomes, but only 19 met all eligibility criteria. KEY FINDINGS: In adults, a significant improvement in full-time employment postsurgery was documented. The ability to drive was significantly increased after surgery and was dependent on seizure freedom. Patients generally perceived improved relationships, independence, and overall lifestyle postsurgery. Marital status generally remained unchanged when compared to controls, education improved modestly, and income/financial status changes depended on how it was assessed (e.g., income level vs. receipt of disability pension). In children, a study examining behavior showed improved social interactions in those who underwent surgery compared to controls. The results for other social outcome categories were more variable. SIGNIFICANCE: Overall, the majority of studies reported improvement in social outcomes after surgery. However, prospective controlled observational studies using objective social outcome measures are necessary prior to making specific conclusions about the influence of surgery on social outcomes other than employment or driving status in all age groups, but particularly in children and the elderly.

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.

Child psychiatry.

This paper first summarizes the main findings of clinical studies conducted over the past two and a half decades on psychopathology (i.e., psychiatric diagnoses, behavior and emotional problems) in children with new onset and chronic epilepsy both with and without intellectual disability who are treated medically and surgically. Although impaired social relationships are core features of the psychiatric disorders found in pediatric epilepsy, few studies have examined social competence (i.e., social behavior, social adjustment, and social cognition) in these children. There also is a dearth of treatment studies on the frequent psychiatric comorbidities of pediatric epilepsy, attention deficit hyperactivity disorder, anxiety disorders, and depression. Drs. Hamiwka and Jones then describe their current and planned studies on social competence and cognitive behavioral treatment of anxiety disorders, respectively, in these children and how they might mitigate the poor long-term psychiatric and social outcome of pediatric epilepsy.

The incidence of injuries in persons with and without epilepsy--a population-based study.

PURPOSE: To compare the 1-year population-based incidence and types of injuries in persons with and without epilepsy. METHODS: Three administrative databases (inpatient visits, physician claims, and emergency room visits) were linked from fiscal years 1996-2003 using a provincial insurance plan registry, which captures 99% of a population of 1.4 million in a large Canadian health region. Epilepsy cases (all age groups) from fiscal year 1996-2002 were identified. Three people without epilepsy were matched to one person with epilepsy for age (±1 year) and sex. Injuries were defined as any of 16 types of injuries for which medical attention was sought that occurred within fiscal year 2003. RESULTS: Eight thousand eight hundred ninety subjects with epilepsy were identified and matched to 26,670 controls for age and sex. The mean age was 37.4 years (range 0.01-96.4 years), and 51.3% of subjects were male. The 1-year incidence of one or more injuries was 20.6% among persons with epilepsy and 16.1% among those without epilepsy (p < 0.001). Of the 16 types of injuries studied, 11 were higher in persons with epilepsy compared to those without epilepsy, and included fractures, crushing injuries, intracranial injuries, other types of head injuries, and multiple injuries. The difference was still significant after adjusting for age, gender, and comorbidities. DISCUSSION: The 1-year incidence of injuries in this study was greater in persons with epilepsy compared to those without epilepsy, for nearly all injury types. Injury prevention should be discussed during routine visits in persons with epilepsy.

Current dipole orientation and distribution of epileptiform activity correlates with cortical thinning in left mesiotemporal epilepsy.

To evaluate cortical architecture in mesial temporal lobe epilepsy (MTLE) with respect to electrophysiology, we analyze both magnetic resonance imaging (MRI) and magnetoencephalography (MEG) in 19 patients with left MTLE. We divide the patients into two groups: 9 patients (Group A) have vertically oriented antero-medial equivalent current dipoles (ECDs). 10 patients (Group B) have ECDs that are diversely oriented and widely distributed. Group analysis of MRI data shows widespread cortical thinning in Group B compared with Group A, in the left hemisphere involving the cingulate, supramarginal, occipitotemporal and parahippocampal gyri, precuneus and parietal lobule, and in the right hemisphere involving the fronto-medial, -central and -basal gyri and the precuneus. These results suggest that regardless of the presence of hippocampal sclerosis, in a subgroup of patients with MTLE a large cortical network is affected. This finding may, in part, explain the unfavorable outcome in some MTLE patients after epilepsy surgery.

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.

Feasibility and clinical utility of early electroencephalogram (EEG) in children with first seizure.

The feasibility and clinical utility of early electroencephalogram (within 48 hours) was studied in 127 children (age, 1 month-17 years) referred for a "first seizure." The electroencephalogram was considered late after 48 hours. Electroencephalogram abnormalities were classified as nonepileptiform or epileptiform. Children were classified as having an "epileptic" or "nonepileptic" event. An early electroencephalogram was obtained in 23 (18%). Late referral (n = 36), weekend event (n = 23), difficulty contacting families (n = 11), parental schedules (n = 9), and laboratory scheduling (n = 11) resulted in late electroencephalograms. All 94 children with an epileptic event had an electroencephalogram, 19 (20%) within 48 hours. Results were abnormal in 9 (47%) early (7 epileptiform, 2 nonepileptiform) and 35 (44%) late (30 epileptiform, 5 nonepileptiform). Increased abnormalities were not seen with early electroencephalography (P = .50). Early electroencephalograms may not be feasible in the pediatric population and did not show a higher yield of abnormalities.

Perceived health in children presenting with a "first seizure".

The goal of this study was to determine health perceptions of children and parents after a "first seizure." Children 5-17 years of age referred with a first recognized seizure (FRS) were included in the study. Children and primary caregivers completed the Child Health Questionnaire. Sixty-seven of 70 (96%) participated (mean age=11.2, SD=3.4; 48 seizure, 19 nonseizure). Parents of children with a first recognized epileptic seizure (FRS-e) had significantly lower scores on Psychosocial Summary scores (P<0.001) and on 6 of 12 subscales. Children who had had their first recognized nonepileptic seizure (FRS-ne) tended to have poorer Parental Time-Emotional scores (P=0.05). Although children did not receive lower scores, they did report a change in perceived health (P=0.017). While parents of children presenting with a FRS report increased emotional impact, those with a FRS-e report more significant difficulties in several domains of perceived health. It is important for physicians and health care providers to be aware of these concerns as they might impact further interventions.

Ambulatory electroencephalography (EEG) in children: diagnostic yield and tolerability.

Sixty-four children, aged 0-17 years, undergoing ambulatory electroencephalography (EEG) were prospectively recruited during a 12-month period. The diagnostic yield of ambulatory electroencephalography was determined for each of the following groups: group 1: differentiation of seizures from nonepileptic events; group 2: determination of seizure/interictal discharge frequency; and group 3: classification of seizure type or localization. The ambulatory electroencephalography answered the clinical question in 61% of group 1 (27/44) and 100% of groups 2 (16/16) and 3 (4/4). Of 44 cases in Group 1, clinical events were recorded in 61%; the ambulatory electroencephalography result changed the diagnosis from epileptic to nonepileptic or vice versa in 27%. When clinicians suspected that events were epileptic, ambulatory electroencephalography changed the clinical impression in 50%, whereas when events were suspected to be nonepileptic, ambulatory electroencephalography confirmed that impression in 83%.

Health behavior in teens with epilepsy: how do they compare with controls?

The goal of the study was to determine if adolescents with epilepsy have poorer health behavior than healthy controls. Health behavior was compared in two cohorts: cognitively normal teens aged 11-16 with epilepsy and similarly aged controls. Teens completed the Health Behaviour in School-Aged Children (HBSC) and Piers-Harris II, and the primary caregiver completed the Family Assessment Measure III. Forty-four teens with epilepsy and 119 orthopedic controls returned questionnaires. Adolescents with epilepsy had poorer health behavior than controls (P<0.003). They felt significantly less positive about their health (P<0.01) and were less physically active (P<0.02). Poorer family function (P<0.05) and lower self-esteem (P<0.001) were predictors of poorer health behavior. Given the increased prevalence of comorbid diseases in adults with epilepsy, clinicians should routinely query teens with epilepsy regarding health behavior and provide anticipatory guidance and appropriate interventions for poor health behavior choices.