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Summary: Objectives: Mutations in the EFHC1 gene have been reported in six juvenile myoclonic epilepsy (JME) families from Mexico and Belize. In this study, we screened 27 unrelated JME Italian families for mutations in the EFHC1 gene. Materials and Methods: Twenty-seven families (86 affected individuals, 52 women) with at least two affected members with JME were selected. DNA was isolated from peripheral blood lymphocytes by standard methods and each exon of the EFHC1 gene was amplified and sequenced using intronic primers. Results: Two heterozygous mutations were identified in three unrelated families. One (R353 W) was a novel missense mutation, while the F229 L mutation was previously described (say which on of the two occurred in two families). Both mutations cosegregated with the disease. In a fourth family, the variant 545GA (resulting in the amino acid substitution R182 H) cosegregated with JME. Conclusions: The results of our study extend the distribution of EFHC1 mutations to the white population and confirm the high level of genetic heterogeneity associated with JME.

Objective: The aim of this study is to test the discriminative capacity of executive function (EF) tasks to better define the cognitive functioning of children with ADHD and comorbidities. Method: One hundred four children were presented with a battery of new EF tasks and a rating scale filled out by parents. Results: Preliminary analysis of the neuropsychological tasks revealed the presence of five factors: Speed of Processing, Inhibition, Planning, Execution, and Retrospective Memory. All children with ADHD were impaired in Execution (a measure describing the capacity to achieve a goal). ADHD-only children were specifically impaired in Planning, while ADHD + reading disorder (RD) children were impaired in Speed of Processing and Retrospective Memory. Children with ADHD + oppositional defiant disorder (ODD) did not show impairment in any other EF domains. The five EF processes correlated with the EF Questionnaire. Conclusion: The present study describes different cognitive profiles in children with ADHD with or without comorbid disorders using neuropsychological EF measures.

Summary: Purpose: To determine the direct costs of epilepsy in a child neurology referral population, stratified by disease, duration, and severity, comparing three different health care settings [i.e., teaching or clinical research (CR) hospitals, general hospitals, and outpatient services]. Methods: Patients were accepted if they had confirmed epilepsy and were resident in the center catchment area. Eligible subjects were grouped in the following categories: (a) newly diagnosed patients; (b) patients with epilepsy in remission; (c) patients with active non–drug-resistant epilepsy; and (d) those with drug-resistant epilepsy. Over a 12-month period, data regarding the consuming of all resources (i.e., consultations, tests, hospital admissions, drugs), were collected for each patient. Using the Italian National Health Service tariffs, the unit cost of each resource was calculated and indicated in Euros, the European currency. Results: A total of 189 patients was enrolled by two teaching-CR hospitals, two general hospitals, and two outpatient services. The patients were evenly distributed across the four categories of epilepsy. The mean annual cost per person with epilepsy was 1,767 Euros. Drug-resistant epilepsy was the most expensive category (3,268 Euros) followed by newly diagnosed epilepsy (1,907 Euros), active non–drug-resistant epilepsy (1,112 Euros), and epilepsy in remission (844 Euros). Costs were generally highest in teaching-CR hospitals and lowest in outpatient services. Hospital services were the major cost in all epilepsy groups, followed by drugs. Conclusions: The cost of epilepsy in children and adolescents in Italy tends to vary significantly depending on the severity and duration of the disease Hospitals services and drugs are the major sources of costs. The setting of health care plays a significant role in the variation of the costs, even for patients in the same category of epilepsy.

Attention-deficit hyperactivity disorder (ADHD) is one of the most common neurobehavioural disorders in children. It has been shown that as many as 85% of patients with ADHD have at least one psychiatric co-morbidity, and approximately 60% have at least two. Atomoxetine is a specific, noradrenergic reuptake inhibitor that provides an effective treatment option for patients with ADHD and co-morbid conditions. The efficacy of atomoxetine in treating ADHD appears to be unaffected by the presence of co-morbid conditions. Therapy with atomoxetine has been associated with statistically significant improvements in symptoms of oppositional defiant disorder in most, but not all, studies. Limited data suggest this agent may have potential in improving co-occurring symptoms of anxiety and may be useful in patients with co-morbid conditions such as tics or Tourette's syndrome. The tolerability profile of atomoxetine in patients with ADHD and co-morbid conditions was similar to that of patients with uncomplicated ADHD. Atomoxetine was well tolerated, with adverse events generally mild and transient; the most frequent adverse events in patients with ADHD included abdominal pain, decreased appetite, nausea and vomiting. The favourable safety and efficacy profile of atomoxetine makes it a promising treatment for patients with ADHD and associated co-morbidities.

Objective: To conduct an open-label, add-on trial on safety and efficacy of levetiracetam in severe myoclonic epilepsy of infancy (SMEI). Patients and Methods: SMEI patients were recruited from different centers according to the following criteria: age ≥3 years; at least four tonic-clonic seizures/month during the last 8 weeks; previous use of at least two drugs. Levetiracetam was orally administrated at starting dose of approximately 10 mg/kg/day up to 50 to 60 mg/kg/day in two doses. Treatment period included a 5- to 6-week up-titration phase and a 12-week evaluation phase. Efficacy variables were responder rate by seizure type and reduction of the mean number per week of each seizure type. Analysis was performed using Fisher exact and Wilcoxon tests. Results: Twenty-eight patients (mean age: 9.4 ± 5.6 years) entered the study. Sixteen (57.1%) showed SCN1A mutations. Mean number of concomitant drugs was 2.5. Mean levetiracetam dose achieved was 2,016 mg/day. Twenty-three (82.1%) completed the trial. Responders were 64.2% for tonic-clonic, 60% for myoclonic, 60% for focal, and 44.4% for absence seizures. Number per week of tonic-clonic (median: 3 vs 1; p = 0.0001 ), myoclonic (median: 21 vs 3; p = 0.002 ), and focal seizures (median: 7.5 vs 3; p = 0.031 ) was significantly decreased compared to baseline. Levetiracetam effect was not related to age at onset and duration of epilepsy, genetic status, and concomitant therapy. Levetiracetam was well tolerated by subjects who completed the study. To date, follow-up ranges 6 to 36 months (mean, 16.2 ± 13.4). Conclusion: Levetiracetam add-on is effective and well tolerated in severe myoclonic epilepsy of infancy. Placebo-controlled studies should confirm these findings.

This was a prospective open comparative pilot study to assess the efficacy and tolerability of first-line vigabatrin monotherapy in childhood partial epilepsies. Two groups of patients were recruited over the same period. The vigabatrin monotherapy group comprised 40 patients (18 male, 22 female; mean age at last visit 7.5 years); the comparative carbamazepine monotherapy group comprised 40 consecutive clinic patients (22 male, 18 female; mean age at last visit 7.8 years). Seizures disappeared in 82% of vigabatrin patients and in all carbamazepine patients with idiopathic partial epilepsy, and in 50% of vigabatrin patients and 55% of carbamazepine patients with symptomatic partial epilepsy. Interictal EEG abnormalities decreased in vigabatrin patients more than in carbamazepine patients (P < 0.05). Tolerability was good in vigabatrin patients, but four out of 37 showed mild irritability by the end of the trial. Persistent sedation was observed in eight of the 40 patients receiving carbamazepine. No patient had drug therapy discontinued because of side-effects. During vigabatrin long-term monotherapy, efficacy and good clinical tolerability were maintained. These results suggest that vigabatrin may be an alternative first-line treatment for childhood partial epilepsies. Further blinded comparative randomized trials are needed.