Gregory B. Sharp

A Comparison of Rectal Diazepam Gel and Placebo for Acute Repetitive Seizures

BACKGROUND Acute repetitive seizures are readily recognizable episodes involving increased seizure frequency. Urgent treatment is often required. Rectal diazepam gel is a promising therapy. METHODS We conducted a randomized, double-blind, parallel-group, placebo-controlled study of home-based treatment for acute repetitive seizures. Patients were randomly assigned to receive either rectal diazepam gel, at a dosage varying from 0.2 to 0.5 mg per kilogram of body weight on the basis of age, or placebo. Children received one dose at the onset of acute repetitive seizures and a second dose four hours later. Adults received three doses -- one dose at onset, and two more doses 4 and 12 hours after onset. Treatment was administered by a care giver, such as a parent, who had received special training. The number of seizures after the first dose was counted for 12 hours in children and for 24 hours in adults. RESULTS Of 125 study patients (64 assigned to diazepam and 61 to placebo) with a history of acute repetitive seizures, 91 (47 children and 44 adults) were treated for an exacerbation of seizures during the study period. Diazepam treatment was superior to placebo with regard to the outcome variables related to efficacy: reduced seizure frequency (P<0.001) and improved global assessment of treatment outcome by the care giver (frequency and severity of seizures and drug toxicity) (P<0.001). Post hoc analysis showed diazepam to be superior to placebo in reducing seizure frequency in both children (P<0.001) and adults (P=0.02), but only in children was it superior with regard to improvement in global outcome (P<0.001). The time to the first recurrence of seizures after initial treatment was longer for the patients receiving diazepam (P<0.001). Thirty-five patients reported at least one adverse effect of treatment; somnolence was the most frequent. Respiratory depression was not reported. CONCLUSIONS Rectal diazepam gel, administered at home by trained care givers, is an effective and well-tolerated treatment for acute repetitive seizures.

Parental anxiety and quality of life in children with epilepsy

Parental beliefs and attitudes concerning epilepsy may significantly impact adjustment and quality of life for both the child and family. The purpose of the present study was to examine the relationship between parental anxiety and quality of life in pediatric patients with ongoing epilepsy. Subjects were parents (n=200) of children between the ages of 6 and 16 years who had been diagnosed and treated for epilepsy for at least 1 year. Parents were given quality of life and anxiety questionnaires during the childs clinic visit. A stepwise regression analysis suggested that severity of comorbid conditions, parental anxiety, seizure control, and number of medications were significantly associated with quality of life for these children. Parents with increased anxiety whose children had poorly controlled seizures and a comorbid disability were found to have diminished quality of life.

Anxiety in children with epilepsy

Although the prevalence is unknown, affective disorders are more common in children with epilepsy than in healthy controls. The purpose of the present study was to examine the occurrence of anxiety in children and adolescents with epilepsy and to determine factors associated with elevation of these symptoms. Children and adolescents (n=101) between the ages of 6 and 16 years were given the Revised Childrens Manifest Anxiety Scale (RCMAS). Mild to moderate symptoms of anxiety were reported by 23% of the patients. Based on regression analysis, factors significantly associated with increased anxiety included the presence of comorbid learning or behavioral difficulties, ethnicity, and polytherapy. Results suggest the need to monitor children and adolescents with epilepsy for affective symptoms in order to provide appropriate interventions.

Cognition and behavior after temporal lobectomy in pediatric patients with intractable epilepsy.

The increased use of surgical intervention for intractable epilepsy during childhood has resulted in a critical need for information concerning possible cognitive and behavioral changes in pediatric patients after surgery. In this pilot study, comprehensive neuropsychologic evaluations were completed on nine children who had a temporal lobectomy for intractable epilepsy before 16 years of age. Performances before and after surgery were compared using cognitive and behavioral measures. Repeated measures analysis of variance did not indicate differences in performance on the basis of laterality of surgery, although the number of left (n = 5) vs right (n = 4) temporal resections was small. Paired comparison t tests, which included all patients, did not suggest marked changes in cognitive functioning after surgery, although decreases in delayed verbal memory were evident. Positive effects on quality of life during the first year after surgical intervention were suggested by reduced internalizing symptoms and increased social interaction. Replication of this study is recommended with a larger number of patients and multicenter collaboration.

Factors Associated with Academic Achievement in Children with Controlled Epilepsy.

Children with epilepsy are at risk for academic underachievement. Multiple etiologies for this academic vulnerability have been suggested by past research including lower self-esteem, inattention, memory inefficiency, and lower socioeconomic status. The present study assessed 65 children (mean age = 10 years, 5 months) with well-controlled epilepsy on the four primary factors, as well as academic achievement and intelligence. A stepwise regression analysis was employed with academic achievement as the dependent variable and measures of self-esteem, attention, memory, and socioeconomic status as independent variables. When intelligence was controlled, attention was the only variable associated with achievement scores. Seizure variables including seizure type and duration of epilepsy were not associated with differences in academic performance. Findings support the importance of measuring attention skills in children with epilepsy and suggest that reduced auditory attention skills may be associated with decreased academic performance in these children.

The neurotoxicity of cyclotrimethylenetrinitramine (RDX) in a child: a clinical and pharmacokinetic evaluation

Cyclotrimethylenetrinitramine (RDX) is a highly explosive compound frequently used for both military and civilian purposes. Previously reported cases of human RDX intoxication were limited to wartime settings and have described no human pharmacokinetic data. We report the first human intoxication to occur in a non-wartime setting. This intoxication presented with status epilepticus in a child and permitted the description of RDX human pharmacokinetics. It also suggested a strong association between central nervous system dysfunction and RDX intoxication.

Nerve Root Enhancement on Spinal MRI in Pediatric Guillain-Barré Syndrome

Guillain-Barré syndrome diagnosis is based on clinical presentation and supportive diagnostic testing. In its early stage, no single, reliable diagnostic test is available. However, a finding of nerve root enhancement on spinal magnetic resonance imaging may be useful. We evaluated the frequency of nerve root enhancement on spinal magnetic resonance imaging in children with Guillain-Barré syndrome. At a single tertiary pediatric center, we conducted a retrospective chart review of children with Guillain-Barré syndrome who had complete spinal or lumbosacral spinal magnetic resonance imaging with gadolinium administration from January 2002-January 2009. Twenty-four consecutive patients were identified. Spinal nerve root enhancement with gadolinium was present in 92% (22/24) of children with Guillain-Barré syndrome on initial spinal magnetic resonance imaging (95% confidence interval, 0.745-0.978). This finding increased to 100% of patients, after two patients underwent repeat spinal magnetic resonance imaging that did reveal nerve root enhancement. Patterns of enhancement were variable, but involved the thoracolumbar nerve roots in all patients. Enhancement of nerve roots with gadolinium on initial spinal magnetic resonance imaging was frequently present in these children with Guillain-Barré syndrome. Spinal magnetic resonance imaging is a sensitive diagnostic test and should be considered an additional diagnostic tool in select cases.

Patterns of memory performance in children with controlled epilepsy on the CVLT-C.

Decreased memory skills have been reported in children with epilepsy. However, standardized instruments to evaluate learning and memory in children have been unavailable until recently. The present study was designed to assess memory patterns in children with epilepsy based on the California Verbal Learning Test-Childrens Version (CVLT-C). The test was administered to 44 children with complex partial seizures and 21 children with generalized seizures between 8 and 13 years of age. Children in the study had been treated for epilepsy for at least 6 months, had well-controlled seizures on monotherapy, and had no evidence of anticonvulsant toxicity. Children with head injuries, learning disabilities, or hyperactivity were excluded. Test results did not reflect differences in memory performance based on seizure type. Scores for the entire sample indicated intact new learning, decreased intrusions and perseverative responses, and better short-term than long-term delayed recall. Recognition skills were stronger than long-term delayed recall skills and suggested that memory performance may be improved for these children when a multiple-choice format is available in academic settings.

The effects of seizure type, level of seizure control, and antiepileptic drugs on memory and attention skills in children with epilepsy

Memory and attention skills were assessed in 84 children with epilepsy who had no documented learning or behavioral disorders. Seizure type, level of control, and antiepileptic drug effects were examined in relation to their influence on memory and attention function. For the entire sample, verbal and visual memory skills were found to be within the average range. However, subtle problems with attentional skills were noted. Two‐way analyses of variance, based on seizure type by level of control, did not indicate significant group differences in memory and attention skills between children with complex partial versus absence seizures. Children with uncontrolled seizures had more difficulty with recall of complex verbal information. A notable finding was that children on polytherapy had significantly lower verbal and visual memory scores than children on monotherapy. Results suggest that children with epilepsy, without learning or behavioral disorders, have intact memory skills but may have subtle difficult...

The course of inattentive and hyperactive–impulsive symptoms in children with new onset seizures

The purpose of the present study was to determine the prevalence of inattentive and hyperactive-impulsive symptoms in children with newly diagnosed epilepsy, explore the course of these symptoms over time, and examine factors associated with change in these symptoms. Parents of children (n=42) were administered the Attention Deficit Disorder Evaluation Scale-Home Version (ADDES-HV) at the time of diagnosis. The ADDES-HV was readministered after the childs seizures were controlled. Prior to initiation of anticonvulsant therapy, 31% of the children were rated as having clinically significant problems with inattention and 31% with hyperactivity-impulsivity. At follow-up, 27% had elevated symptoms of inattention and 24% had hyperactivity-impulsivity. Analysis of this change indicated that children with a normal MRI were more likely to have decreased hyperactive-impulsive behaviors following control of their seizures. Results suggest the need for assessment and monitoring of attention in children with epilepsy.