Penelope K. Manasco

Lamotrigine for generalized seizures associated with the Lennox-Gastaut syndrome. Lamictal Lennox-Gastaut Study Group.

BACKGROUND The Lennox-Gastaut syndrome, a severe form of epilepsy that usually begins in early childhood, is difficult to treat. Dose-related drug toxicity is common. METHODS We conducted a double-blind, placebo-controlled trial of the antiepileptic drug lamotrigine in patients with the Lennox-Gastaut syndrome. Eligible patients had more than one type of predominantly generalized seizure, including tonic-clonic, atonic, tonic, and major myoclonic, and had seizures on average at least every other day. After a 4-week base-line period in which all participants received placebo, we randomly assigned 169 patients (age range, 3 to 25 years) to 16 weeks of lamotrigine (n= 79) or placebo (n=90) in addition to their other antiepileptic drugs. RESULTS The median frequency of all major seizures changed from base-line levels of 16.4 and 13.5 per week in the lamotrigine and placebo groups, respectively, to 9.9 and 14.2 per week after 16 weeks of treatment (P=0.002). Thirty-three percent of the patients in the lamotrigine group and 16 percent of those in the placebo group had a reduction of at least 50 percent in the frequency of seizures (P= 0.01). There were no significant differences between groups in the incidence of adverse events, except for colds or viral illnesses, which was more common in the lamotrigine group (P=0.05). CONCLUSIONS Lamotrigine was an effective and well-tolerated treatment for seizures associated with the Lennox-Gastaut syndrome.

Lamotrigine for Generalized Seizures Associated with the Lennox–Gastaut Syndrome

Background The Lennox–Gastaut syndrome, a severe form of epilepsy that usually begins in early childhood, is difficult to treat. Dose-related drug toxicity is common. Methods We conducted a double-blind, placebo-controlled trial of the antiepileptic drug lamotrigine in patients with the Lennox–Gastaut syndrome. Eligible patients had more than one type of predominantly generalized seizure, including tonic–clonic, atonic, tonic, and major myoclonic, and had seizures on average at least every other day. After a 4-week base-line period in which all participants received placebo, we randomly assigned 169 patients (age range, 3 to 25 years) to 16 weeks of lamotrigine (n = 79) or placebo (n = 90) in addition to their other antiepileptic drugs. Results The median frequency of all major seizures changed from base-line levels of 16.4 and 13.5 per week in the lamotrigine and placebo groups, respectively, to 9.9 and 14.2 per week after 16 weeks of treatment (P = 0.002). Thirty-three percent of the patients in the lam...

Effects of luteinizing hormone-releasing hormone agonists on final height in luteinizing hormone-releasing hormone-dependent precocious puberty

Children with precocious puberty have accelerated skeletal maturation, which often leads to short adult height (1 -4). Long-acting luteinizing hormone-releasing hormone (LHRH) agonist treatment of LHRH-dependent precocious puberty decreases gonadotrophin and sex steroid levels and improves predicted adult height (5-33). This paper will consider the historical data on the natural history of final height in untreated children with precocious puberty, review the data on predicted height in children with precocious puberty treated with LHRH agonists, and finally review the data on the final height of children treated with LHRH agonists, including the first 44 children to reach adult height after treatment with deslorelin at the National Institutes of Health, USA.

A Novel Testis-Stimulating Factor in Familial Male Precocious Puberty

BACKGROUND Familial male precocious puberty is a gonadotropin-independent form of precocious puberty that occurs only in males. The cause of the disorder is unknown. To examine the hypothesis that the plasma of boys with familial male precocious puberty contains a novel stimulator of testicular testosterone production, we developed a bioassay using adult male cynomolgus monkeys. METHODS We collected plasma from 12 boys with familial male precocious puberty, 7 normal prepubertal boys of similar ages and with similar plasma gonadotropin levels, and 1 boy with hypogonadotropic hypogonadism and infused it into the testicular artery of adult male cynomolgus monkeys that had been pretreated with gonadotropin-releasing-hormone antagonist to inhibit the endogenous secretion of gonadotropins. Testicular venous effluent was collected at 15-minute intervals for 3 or 5 hours for the measurement of testosterone. RESULTS The mean (+/- SE) peak testosterone response, as compared with base line, was significantly greater in the monkeys infused with plasma from the 12 boys with familial male precocious puberty than in the monkeys infused with plasma from the 7 normal prepubertal boys and the boy with hypogonadotropic hypogonadism (385 +/- 51 vs. 184 +/- 25 percent, P less than 0.005) in the three-hour studies. Plasma from 92 percent of the boys with familial male precocious puberty and 12.5 percent of the normal prepubertal boys stimulated a response greater than 195 percent of base-line values. In the animals studied for five hours after receiving a second dose of antagonist, the mean peak testosterone response, as compared with base line, was significantly greater in the monkeys infused with plasma from three boys with familial male precocious puberty than in the monkeys infused with plasma from three normal prepubertal boys (363 +/- 81 vs. 115 +/- 6 percent, P less than 0.01). The mean area under the testosterone-response curve was significantly larger in the monkeys infused with plasma from the boys with familial male precocious puberty in the five-hour studies (154 +/- 34 vs. -58 +/- 10 percent, P less than 0.005), but not in the three-hour studies. CONCLUSIONS These findings support the presence of a circulating testis-stimulating factor in the plasma of boys with familial male precocious puberty. The production of such a factor would explain the biologic nature of the disorder.