Bone mineral density in children, adolescents, and young adults with epilepsy.

PURPOSE: The aim of this study was to assess bone mineral density (BMD) in a large population of children, adolescents, and young adults with epilepsy alone or in association with cerebral palsy and/or mental retardation. METHODS: Ninety-six patients were enrolled in the study. The group comprised 50 males and 46 females, aged between 3 and 25 years (mean age 11 years). The control group consisted of 63 healthy children and adolescents (23 males, 40 females), aged between 3 and 25 years (mean age 12.1 years). Patients underwent a dual-energy x-ray absorptiometry (DEXA) scan of the lumbar spine (L1-L4) and the z scores were calculated for each patient; the t score was considered for patients 18 years of age or older. RESULTS: Abnormal BMD was found in 56 patients (58.3%), with values documenting osteopenia in 42 (75%) and osteoporosis in 14 (25%). A significant difference emerged between epileptic patients and the control group in BMD, z score, and body mass index (BMI) (p = <0.001). Lack of autonomous gait, severe mental retardation, long duration of antiepileptic treatment, topiramate adjunctive therapy, and less physical activity significantly correlated with abnormal BMD. DISCUSSION: This study detected abnormal BMD in more than half of a large pediatric population with epilepsy with or without cerebral palsy and/or mental retardation. The clinical significance of these findings has yet to be clarified.

Topiramate in children and adolescents with epilepsy and mental retardation: a prospective study on behavior and cognitive effects.

The aim of the present study was to assess the behavioral and cognitive effects following treatment with topiramate in children and adolescents with epilepsy with mild to profound mental retardation. The study group comprised 29 children, 16 males and 13 females, aged 3 to 19 years, affected by partial (4) and generalized (25) crypto/symptomatic epilepsy and mental retardation (7 mild, 5 moderate, 15 severe, 2 profound), who were administered topiramate (TPM) as add-on therapy to their baseline antiepileptic treatment. At baseline, 3 months, 6 months, and 12 months, parents or caregivers of each patient were administered a questionnaire based on the Holmfrid Quality of Life Inventory. After a 3-month follow-up, the add-on topiramate caused overall mild to moderate cognitive/behavioral worsening in about 70% of children and adolescents with mental retardation and epilepsy. After 6 and 12 months of follow-up, global worsening persisted in 31 and 20.1% of cases, respectively. In conclusion, this trial confirms that TPM can have significant adverse cognitive and behavioral side effects, even in mentally disabled children and adolescents.

Bone mineral density in angelman syndrome.

Our aim was to evaluate bone mineral densitometry in patients with Angelman syndrome with or without antiepileptic therapy. Eighteen patients (9 females, 9 males), aged 4.0-24.3 years (mean age, 10.1 years), and two control groups consisting of 18 epileptic and 24 healthy patients, underwent dual-energy X-ray absorptiometry at the lumbar spine (L(1)-L(4)), and z score was evaluated for each patient; the t score was considered for patients aged > or = 18 years. Abnormal bone mineral density was present in 8/18 (44.5%) of patients with Angelman syndrome, in 7/18 (38.9%) of the epileptic group, and in none of the healthy controls. Furthermore, a significant difference regarding mean age of patients (6 versus 15 years, P = 0.008, by Fisher exact test), and mean length of drug treatment (3.5 versus 11.1 years, P = 0.005 by Fisher exact test), appeared in the group with Angelman syndrome. Most of these patients (94.4%) were receiving antiepileptic drugs, mainly valproic acid, for many years. In conclusion, our study revealed osteopenia in almost half the children and young patients with Angelman syndrome. Dual-energy X-ray absorptiometry should be performed in all patients with Angelman syndrome, particularly if they are treated with antiepileptic drugs.

Temporal lobe dual pathology in malignant migrating partial seizures in infancy.

A child had the characteristic clinical and EEG pattern of migrating partial seizures in infancy with left temporal lobe atrophy, hippocampal sclerosis and cortical-subcortical blurring. Seizures were drug-resistant, with recurring episodes of status epilepticus. The child developed microcephaly with arrest of psychomotor development. Focal brain lesions, in the context of migrating partial seizures, have not been previously reported.[Published with video sequences].

Plasma free carnitine in epilepsy children, adolescents and young adults treated with old and new antiepileptic drugs with or without ketogenic diet.

This study was performed to evaluate carnitine deficiency in a large series of epilepsy children and adolescents treated with old and new antiepileptic drugs with or without ketogenic diet. Plasma free carnitine was determined in 164 epilepsy patients aged between 7 months and 30 years (mean 10.8 years) treated for a mean period of 7.5 years (range 1 month-26 years) with old and new antiepileptic drugs as mono or add-on therapy. In 16 patients on topiramate or lamotrigine and in 11 on ketogenic diet, plasma free carnitine was prospectively evaluated before starting treatment and after 3 and 12 months, respectively. Overall, low plasma levels of free carnitine were found in 41 patients (25%); by single subgroups, 32 out of 84 patients (38%) taking valproic acid and 13 of 54 (24%) on carbamazepine, both as monotherapy or in combination, showed low free carnitine levels. A higher though not statistically significant risk of hypocarnitinemia resulted to be linked to polytherapy (31.5%) versus monotherapy (17.3%) (P=.0573). Female sex, psychomotor or mental retardation and abnormal neurological examination appeared to be significantly related with hypocarnitinemia, as well. As to monotherapy, valproic acid was associated with a higher risk of hypocarnitinemia (27.3%) compared with carbamazepine group (14.3%). Neither one of the patients on topiramate (10), lamotrigine (5) or ketogenic diet (11) developed hypocarnitinemia during the first 12 months of treatment. Carnitine deficiency is not uncommon among epilepsy children and adolescents and is mainly linked to valproate therapy; further studies are needed to better understand the clinical significance of serum carnitine decline.

Lamotrigine versus valproic acid as first-line monotherapy in newly diagnosed typical absence seizures: an open-label, randomized, parallel-group study.

PURPOSE: To compare the efficacy of lamotrigine (LTG) and valproic acid (VPA) in newly diagnosed children and adolescents with typical absence seizures. METHODS: A randomized, open-label parallel-group design was used. After undergoing an awake video-EEG recording, which included one to two trials of 3 min of hyperventilation and intermittent photic stimulation, eligible patients were randomized to receive LTG or VPA. LTG was initiated at a daily dose of 0.5 mg/kg for 2 weeks in two divided doses, followed by 1.0 mg/kg/day for an additional 2 weeks. Thereafter, doses were increased in 1-mg/kg/day increments every 5 days until seizures were controlled, intolerable adverse effects occurred, or a maximum dose of 12 mg/kg/day had been reached. VPA was equally uptitrated according to clinical response, starting at 10 mg/kg and increasing by 5 mg/kg/24 h every 3 days, if required, to a maximum of 30 mg/kg/day in three divided doses. Patients were seen in the clinic every month for < or = 12 months. The primary efficacy end point at each visit was seizure freedom, defined as lack of clinically observed seizures since the previous visit and lack of electroclinical seizures during ambulatory 24-h EEG testing and a video-EEG session with hyperventilation. RESULTS: Thirty-eight children (17 boys, 21 girls), aged from 3 to 13 years (mean, 7.5 years), all newly diagnosed with childhood or juvenile typical absence seizures, were enrolled. After 1 month of treatment, 10 (52.6%) of 19 children taking VPA and one (5.3%) of 19 taking LTG were seizure free (p = 0.004). By the 3-month follow-up, 12 (63.1%) children taking VPA and seven (36.8%) taking LTG were controlled (p = 0.19). After 12 months, 13 children taking VPA (dose range, 20-30 mg/kg/day; mean serum level, 76.8 mg/L; range, 51.4-91 mg/L) and 10 taking LTG (dose range, 2-11 mg/kg/day; mean serum level, 8.1 mg/L; range, 1.1-18 mg/L) were seizure free (p = 0.51). Side effects were mostly mild and transient and were recorded in two (10.6%) children treated with VPA and in six (31.8%) treated with LTG. CONCLUSIONS: Both VPA and LTG can be efficacious against absence seizures, although VPA shows a much faster onset of action, at least in part because of its shorter titration schedule.