Abstract: Following a previous preliminary report on a group of children suffering from partial epilepsies, we present the final considerations on the same group in order to evaluate the long-term efficacy, tolerability and safety of oxcarbazepine (OXC). We enrolled 36 patients (mean age 8.5), between January 2003 and December 2004, with new diagnosis of partial epilepsy: 25 patients were affected by idiopathic partial epilepsy, eight by symptomatic epilepsy and three by cryptogenic epilepsy. Each patient was scheduled to attend the center four times after the initial examination: 3 months (T1), 12 months (T2), 24 (T3) months and 36 (T4) months after the beginning of OXC-monotherapy (T0). At the end of our study, 20 patients were seizure free (SF): nine stopped OXC because of SF for at least 2 years, 11 were still on therapy. One patient showed a reduction of seizure frequency >/=50%, three were non responders (but still on therapy), nine stopped OXC due to a non-responder condition during follow-up before T4 and one because of adverse effects. At the end of the study no EEG focal abnormalities became generalized because of treatment. Normalization of EEG was observed in ten patients. Our preliminary findings have been confirmed. OXC can be considered an effective and well tolerated first line drug for long-term monotherapy in children with epilepsy, both for idiopathic and symptomatic/cryptogenic forms.

Abstract: OBJECTIVE: This study evaluates the effects of long-term carbamazepine (CBZ) and valproate acid (VPA) therapy on thyroid function in epileptic children. DESIGN: A prospective study performed in 32 newly diagnosed pediatric patients, subdivided into two groups: 18 patients treated with CBZ and 14 patients treated with VPA. Thirty-two sex- and age- matched subjects served as controls. METHODS: Serum TSH, thyroxine (T(4)), triiodothyronine (T(3)), free thyroxine (fT(4)), free triiodothyronine (fT(3)), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (TG-Ab) were evaluated at baseline and at the 3rd, 6th, and 12th month in all patients and in the control group. A TRH stimulation test was performed in all epileptic patients at baseline and at the 3rd, 6th, and 12th month evaluations while in controls only baseline assessment was carried out. RESULTS: At baseline evaluation, thyroid function was normal in all epileptic children. After 3 months, CBZ-treated patients showed serum T(4) and fT(4) levels significantly lower than baseline evaluation and control subjects. Serum T(4) and fT(4) concentrations were unaffected by VPA monotherapy. Serum T(3) and fT(3) were normal in both CBZ-treated and VPA-treated patients. TRH test was normal in all patients. At 6th and 12th month evaluations, the same alterations were present in CBZ-treated patients while thyroid function remained normal in VPA-treated patients. TRH test responses were normal in all epileptic patients. TPO-Ab and TG-Ab were always absent in all patients. CONCLUSIONS: Our data suggest that VPA monotherapy does not alter thyroid hormones. On the contrary, alterations of thyroid hormones occur in CBZ-treated children. However, the patients are euthyroid and thyroid hormone alterations are not associated with clinical or subclinical hypothyroidism.

Abstract: The neuronal ceroid lipofuscinoses (NCL) are a group of genetically heterogeneous neurodegenerative disorders. The recent identification of the MFSD8/CLN7 gene in a variant-late infantile form of NCL (v-LINCL) in affected children from Turkey prompted us to examine the relative frequency of variants in this gene in Italian patients with v-LINCL. We identified nine children harboring 11 different mutations in MFSD8/CLN7. Ten mutations were novel and included three nonsense (p.Arg35Stop, p.Glu381Stop, p.Arg482Stop), four missense (p.Met1Thr, p.Gly52Arg, p.Thr294Lys, p.Pro447Leu), two splice site mutations (c.863+3_4insT, c.863+1G>C), and a 17-bp deletion predicting a frameshift and premature protein truncation (c.627_643del17/p.Met209IlefsX3). The clinical phenotype, which was similar to that of the Turkish v-LINCL cases, was not influenced by type and location of the mutation nor the length of the predicted residual gene product. As well as identifying novel variants in MFSD8/CLN7, this study contributes to a better molecular characterization of Italian NCL cases, and will facilitate medical genetic counseling in such families. The existence of a subset of v-LINCL cases without mutations in any of the known NCL genes suggests further genetic heterogeneity.

Abstract: PURPOSE: To report on the first multicenter Italian experience with zonisamide as an add-on drug for refractory generalised or partial epilepsy in children, adolescents and young adults. METHODS: The patients were enrolled in a prospective, add-on, open-label treatment study from eight Italian centres for children and adolescent epilepsy care. Eighty-two young patients (45 males, 37 females), aged between 3 and 34 years (mean 13.1 years), all affected by partial (47) or generalised (35) refractory epilepsy, were enrolled in the study. ZNS was added to the baseline therapy at a starting dose of 1 mg/kg/day twice daily. This dose was increased by 2 mg/kg every 1-2 weeks over a period of up 3 months, according to the patient's response and tolerability, up to a maximum dose of 12 mg/kg. ZNS was given at the mean daily dose of 5.7/mg/kg/24 h (range 1-12 mg/kg). RESULTS: After a mean follow-up period of 11.9 months (range 2-64 months), 9 patients (10.9%) were seizure-free. The number of seizures decreased by 50-99% in 31 cases (37.8%), by 25-49% in 5 cases (6.1%), remained the same in 29 cases (35.4%) and increased in 8 cases (9.7%). After 15 months of follow-up, 61 patients (74.4%) were still taking ZNS, while the remaining 21 (25.6%) had stopped. Twenty-two patients (26.8%) reported adverse effects while taking ZNS. They generally appeared during the first weeks of treatment, and were mild to moderate. The most frequent adverse effects were irritability and a reduced appetite. CONCLUSION: ZNS effectively reduced seizure frequency in this pediatric population with both partial and generalised crypto/symptomatic refractory epilepsy. Its overall tolerability was good.

Abstract: A retrospective multicentre study was performed to analyse psychogenic non-epileptic seizures (PNES) in prepubertal and pubertal patients with idiopathic epilepsy and to determine whether have different clinical characteristics. In this study, we reviewed 36 patients from six neurological referral centres: Department of Pediatrics, Chieti (3 patients); Department of Child Neuropsychiatry, Naples (9 patients); Department of Child Neuropsychiatry, Bologna (8 patients); Department of Neuroscience, Tor Vergata University, Rome (3 patients); Department of Pediatrics, La Sapienza University, Rome (5 patients); and Department of Pediatrics, Siena (8 patients). The population was divided according to Tanner'stages into 14 prepubertal (group I) and 22 pubertal (group II) patients. The two groups were compared on several variables examining the differences between them. The most frequent clinical manifestations in group I were unresponsive events, whereas in group II, motor events were exhibited more significantly. Mood disorders, including major depression, appeared more frequently in pubertal group, but this did not reach a significant difference. Among the psychosocial stressors, fear of rejection and need for attention were the predominant types in the prepubertal patients. The findings of this study reveal some similarities and differences between prepubertal and pubertal patients, which might help to identify predictive factors in patients affected by idiopathic epilepsy who can develop PNES.

Abstract: IN ORDER TO EVALUATE THE PSYCHIATRIC SYMPTOMS ASSOCIATED WITH A DIAGNOSIS OF EATING DISORDERS (ED) WE HAVE ADMINISTERED A NEW PSYCHOMETRIC INSTRUMENT: the Self Administrated Psychiatric Scales for Children and Adolescents (SAFA) test. SAFA was administered to a cohort of 97 patients, aged from 8.8 to 18, with an ED diagnosis. Age, body mass index (BMI) and BMI standard deviation score were analyzed. Furthermore, while looking for linkable risk factors, we evaluated other data that took an influence over the SAFA profile, like parental separation and family components' number. Compared to the range of statistical normality (based on Italian population), patients with bulimia nervosa or binge-eating disorder showed higher and pathologic values in specific subscales. When analyzing sex, males showed more pathologic values in most anxiety-related, obsessiveness-compulsiveness-related and insecurity subscales. A correlation among age, BMI and specific subscales (low self esteem, psychological aspects) emerged in participants with anorexia nervosa. In order to plan more appropriate diagnostic and therapeutic approaches in children or adolescents suffering from ED, the SAFA test can be an important instrument to evaluate psychiatric symptoms. Therefore, we propose to include this useful, simple self-administered test as a new screening tool for ED diagnosis.

Abstract: The aim of this study was to evaluate the efficacy and tolerability of levetiracetam (LEV) monotherapy in juvenile myoclonic epilepsy (JME). The study group consisted of 32 patients with epilepsy (20 males, 12 females) with a mean age of 13 years 3 months (SD 7y 11mo) at seizure onset. LEV was administered as the first drug; all patients were followed up at 6 and 12 months. The dose that achieved seizure control ranged from 1000 to 2500mg/daily. At 6-month evaluation: 15 patients were seizure free; 14 patients were responders (>50% reduction in seizures); and three patients had marginal effects (<50% reduction of seizures). At 12-month evaluation: 29 patients were seizure free; three patients were responders. No patients reported adverse events. These data provide preliminary evidence that LEV may be effective for treating patients with newly diagnosed JME.

Abstract: Topiramate (TPM) is a new, effective and safe antiepileptic drug. TPM is also effective in treating a wide spectrum of conditions such as eating disorders and related anomalies, bulimia nervosa and other conditions in which serotonin (5-hydroxytryptamine, 5-HT) is involved pathogenetically. Plasma serotonin mainly derives from blood platelets, which represent a valid model of serotoninergic neurons. We measured plasma 5-HT levels in 12 children affected by epilepsy who underwent TPM therapy. Inclusion criteria were (i) age range 2-12 years, (ii) weight greater than 12 kg, (iii) no more than one antiepileptic drug used when TPM therapy was instituted, and (iv) a minimum study period of 3 months. After a mean period of 3 months of TPM treatment, a significant increase in mean plasma serotonin levels was observed with respect to the basal levels and those of a control group. There were no significant correlations between the changes in serotonin concentrations and the antiepileptic efficacy or doses of TPM used. TPM may influence serotonin metabolism in children affected by epilepsy. Further studies are needed to establish whether these serotonin plasma changes represent an epiphenomenon or indicate direct effects of TPM on the serotoninergic system.

Abstract: The aim of the study was to assess the efficacy, tolerability, and safety of levetiracetam therapy in children and adolescents with absence epilepsy. Twenty-one participants (11 male, 10 female) with typical absence seizures were enrolled in this prospective study from seven centres in Italy. The mean age and age range at time of enrollment into the study were 8 years 9 months (SD 0.9) and 5 years 1 month to 13 years respectively. All patients were carefully evaluated at 6 months from baseline, and 12 patients were also re-evaluated at 12 months after the beginning of therapy with levetiracetam. At the 6-month evaluation, out of 21 patients studied, 11 were seizure free and one showed 'decreased' seizures (more than 50% reduction in seizures). A less than 50% reduction in seizures was observed in nine patients. At the 12-month evaluation, 10 patients were completely seizure free and two were seizure free with some anomalies in electroencephalograms. Two patients who had shown no improvement at 6 months had decreased seizures at the second follow-up. Our results suggest that monotherapy with levetiracetam could be effective and well tolerated in patients with childhood absence epilepsy and juvenile absence epilepsy. Prospective, large, long-term double-blind studies are needed to confirm these findings.

Abstract: BACKGROUND AND PURPOSE: To review our experience of the efficacy and tolerability of felbamate in children younger than 4 years. METHODS: We used a retrospective chart review to identify 53 children with seizures who were younger than 4 years. Efficacy was evaluated based on the occurrence of responsiveness, defined as seizure frequency reduction of more than 50% for a minimum period of 4 months. Tolerability was based on parent-reported side effects. RESULTS: Twenty-two (41%) patients resulted to be responders and 31 (59%) did not. By univariate analysis, those achieving seizure remission were probably much older, to have a shorter history of epilepsy and a lower frequency of seizures before felbamate therapy. The number of antiepileptic drugs (AEDs) used before felbamate therapy was the only significant predictor of the duration of response to felbamate, with a longer responsiveness to the drug seen in those who were placed under fewer than three AEDs before felbamate compared with those who had taken more than three (median, 16 months vs. 7 months; P < 0.0084). Side effects occurred in 30% of the subjects, but these did not require discontinuation of the drug. DISCUSSION: Felbamate is an effective medication for a wide range of epilepsy syndromes in children younger than 4 years. Although caution is necessary when the drug is used in children, felbamate might represent a possible option for the treatment of epilepsy in this age group.