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Purpose: To determine whether long-term treatment with valproate (VPA) and/or lamotrigine (LTG) in children with epilepsy is associated with altered growth and/or bone metabolism., Methods: Twenty-seven boys and 26 girls, aged 3 to 17 years (9.2 +/- 3.9, mean +/- SD), with epilepsy treated with VPA and/or LTG for > or =2 years were evaluated for growth, nutrient intakes, physical activity, bone mineral density (BMD), and blood biochemical indices of mineral and bone metabolism., Results: Twenty-three (43.4%) of the children had a body height below the 10th percentile. Z-scores for BMD below -1.5 occurred in 24.4% of the children. When patients were divided into two groups according to daily activity score, a significantly lower Z-score for total body BMD (p = 0.007), percentile for body height (p = 0.05), and plasma parathyroid hormone (PTH; p = 0.04), osteocalcin (p = 0.04) and 25-hydroxyvitamin D (25OHD) (p = 0.01) were found in the inactive compared with the active group. Z-score for total body BMD was correlated with daily activity score (r = 0.43, p = 0.008). Plasma intact osteocalcin and intact PTH values correlated significantly (r = 0.36, p = 0.02). Plasma 1,25-dihydroxyvitamin D was within normal range for all subjects. When patients were divided into LTG-alone, VPA-alone, and LTG-plus-VPA treatment groups, significantly lower (p < 0.05) plasma osteocalcin and percentile for body height were found in the VPA-plus-LTG treatment group., Conclusions: Long-term VPA and LTG therapy, particularly when combined, is associated with short stature, low BMD, and reduced bone formation. These alterations may be mediated primarily through reduced physical activity rather than through a direct link to the VPA and/or LTG therapy.

This study aimed to determine whether sodium valproate (VPA) improves cognitive performance and behaviour in children with learning and behavioural problems associated with electrographic epileptiform discharges but without clinical seizures. A randomized, double-blind, single-crossover trial was carried out with VPA or placebo on eight participants with different learning and behaviour problems. Participants also underwent neuropsychological testing under video EEG and the parent and teacher Behaviour Check List (CBCL; Achenbach 1991a, b) during each treatment phase. Clinically none of the children improved on VPA. On formal testing children were more distractable, had increased delay in response time, and showed lower memory scores while on VPA. In addition, parents reported higher internalizing scores on the CBCL while children were on VPA. Our data do not support the use of VPA in similar patients.

Objectives: To study the effectiveness and safety of topiramate in clinical practice, for a group of patients with childhood onset epilepsy., Methods: All patients treated with topiramate at the three study centers between November 1995 and December 31, 1997 were analyzed retrospectively, using a standardized study protocol. Data were gathered on demographic features, seizures response and medication related adverse events., Results: Eighty-seven patients were treated with topiramate. Over 90% seizure reduction was achieved in 8 (9%) patients, 50%-90% in 21 (24%), < 50% in 54 (62%) patients. Four patients (5%) had a deterioration in seizure control. Adverse events required topiramate discontinuation in 36 (41%). Of these 27 (31%) complained of unacceptable cognitive dulling. The rate of dose escalation and final dose in mg/kg were similar in those who remained on topiramate and those who were intolerant because of cognitive side effects., Conclusions: Although topiramate resulted in > 50% seizure reduction in 29 (33%) of this group of patients with difficult epilepsy, its usefulness was limited by a high incidence of adverse effects. Adverse events prevented ongoing therapy for 36 (41%) and cognitive dulling resulted in topiramate discontinuation by 27 (31%) of the group.

Purpose: To compare the cognitive and behavioural effects of clobazam versus standard monotherapy in the treatment of childhood epilepsy., Methods: A randomized, double-blind, prospective design was carried out at three Canadian pediatric epilepsy centres. This study was part of a larger multi-centre study on the efficacy of clobazam. Children with newly diagnosed epilepsy were assigned randomly to receive clobazam or carbamazepine. Children who had failed previous treatment with carbamazepine were assigned randomly to clobazam or phenytoin. Children who had failed on any other antiepileptic drug were assigned randomly to receive clobazam or carbamazepine. In a subset of patients neuropsychological assessments were carried out at 6 weeks and 12 months after initiation of medication. Intelligence, memory, attention, psychomotor speed, and impulsivity were assessed., Results: There were no differences between the clobazam and standard monotherapy groups on any of the neuropsychological measures obtained at 6 weeks or 12 months. There was no evidence for a deterioration in performance for those children who remained on clobazam for the entire 12-month study period., Conclusion: The cognitive and behavioural effects of clobazam appear to be similar to those of standard monotherapy.

We report our experience with add-on clobazam therapy over a 5-year period in 63 children with refractory epilepsy. The mean duration of epilepsy was 6.7 years. Children were followed for 15 to 64 months. Of 63 children, 57 were developmentally delayed, and 54 had a symptomatic/cryptogenic epilepsy. Forty-one percent became either seizure free or had a greater than 90% reduction in seizure frequency. Seizure frequency was reduced 50% to 90% in another 24%. The average daily dose of clobazam was 0.8 mg/kg. Thirty-five percent had the medication withdrawn for persistent or unacceptable side effects or the development of tolerance (seven patients). Side effects included severe aggressive outbursts, hyperactivity, insomnia, and depression with suicidal ideation. Clobazam is a useful add-on medication for 65% of children with epilepsy. Clinical utility may be limited by behavioral side effects in some patients.

Seven of 63 children (11%) treated with clobazam (CLB) for refractory epilepsy developed a severe behavior disorder. This disorder was characterized by aggressive agitation, self injurious behavior, insomnia, and incessant motor activity occurring between 10 and 55 days after initiation of drug therapy. The affected children were relatively young (mean age 6.4 years) and developmentally disabled (four were autistic and two had isolated mental retardation). The disorder occurred with a short latency after initiation of therapy and at a relatively low dosage of CLB. Serum levels of other coadministered antiepileptic drugs were unchanged by the administration of CLB. One child was taking CLB monotherapy. This behavioral deterioration required the discontinuation of CLB, after which patients returned to their previous behavior within 3 weeks. After > 3 years of follow-up all children continue to require multiple antiepileptic drugs but have not had a recurrence of this aggressive agitation. The mechanism of the behavioral change is unclear.