Atomoxetine Treatment of Attention Deficit/Hyperactivity Disorder Symptoms in 3-6-Year-Old Children with Autism Spectrum Disorder: A Retrospective Cohort Study.

Atomoxetine is indicated for the management of attention deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6 to 18 years. Few studies have assessed the safety and tolerability of atomoxetine in younger patients. This retrospective cohort study included 133 children aged 3-6 years who were diagnosed with ADHD comorbid with autism spectrum disorder (ASD). The primary endpoint was the evaluation of the safety profile of atomoxetine. In total, 50 patients (37.6%) experienced adverse events (AEs), which led to treatment discontinuation in 23 patients (17.3%). The most common AEs were gastrointestinal (24.1%), aggression or hostility (12.8%), and increased hyperactivity (9.0%). In the 23 patients who discontinued treatment, all the AEs resolved after treatment ceased. Among the 110 patients who completed at least 6 months' treatment, atomoxetine titrated to a dose of 1.2-1.8 mg/kg/day appeared to be well tolerated and effective. The Clinical Global Impression-Improvement score improved to 1 ("very much improved") and 2 ("much improved") in 62.4% and 20.3% of children, respectively, at their last visit. Overall, atomoxetine appeared to be well tolerated in younger children with comorbid ADHD and ASD. Nevertheless, close patient monitoring remains essential, and the study limitations necessitate caution in generalizing these findings to broader populations. Long-term prospective studies are required.

Infantile and early childhood masturbation: Sex hormones and clinical profile.

BACKGROUND AND OBJECTIVES: Few studies have explored the hormonal triggers for masturbation in infants and young children. Thus, we aimed to study the sex hormones and clinical profiles of masturbating infants and young children. METHODS: This case-control study involved infants and young children who masturbate and were referred to three pediatric neurology clinics between September 2004 and 2006 (n=13), and a similar control group. All children underwent basic laboratory investigations prior to referral. Other tests included electroencephalography (n=8) and brain neuroimaging (n=9). We measured dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, free testosterone, estradiol, dehydroepiandrosterone, sex hormone-binding globulin (SHBG), and androstenedione in all participants. RESULT: The median age at the first incident was 19.5 months (range, 4-36 months); the median masturbation frequency, 4 times/day; and the median duration of each event, 3.9 min. The subjects masturbated in both prone (n=10) and supine positions (n=3); two subjects used the knee-chest position. All subjects showed facial flushing; 6, friction between the thighs; 5, sweating; 9, sleeping after the event; and 12, disturbance on interruption. EEG was abnormal in one of eight subjects tested, and neuroimages were normal in all of nine subjects examined. The case and control groups had comparable levels of all sex hormones, except estradiol, which showed significantly lower levels in the case group (P=.02). CONCLUSION: Masturbation in children seems to be associated with reduced estradiol levels, but not with other sex hormones. Further studies are needed to confirm our findings.

Association between polymorphisms of the DBH and DAT1 genes and attention deficit hyperactivity disorder in children from Jordan.

Attention deficit hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders in children. In this study, the association between 10-repeats in the DAT1 gene and the (GT)n repeat in the DBH gene and ADHD was examined in children from Jordan. In addition, the levels of dopamine-ß-hydroxylase enzyme activity in the plasma of ADHD children were evaluated. Fifty children with ADHD and 50 age- and gender-matched control subjects were recruited. The results showed significant differences between the ADHD group and controls with respect to the plasma levels of dopamine-ß-hydroxylase enzyme activity (25.4±2.3 vs. 84.7±5.0 µmol/min; p<0.01). Moreover, the 10-repeat DAT1 gene and (GT)n DBH gene polymorphisms were significantly associated with ADHD development (p<0.05). In conclusion, the DBH and DAT1 genes appear to play a role in the development of ADHD in the Jordanian population.

A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome.

Progressive myoclonus epilepsy (PME) is a syndrome characterized by myoclonic seizures (lightning-like jerks), generalized convulsive seizures, and varying degrees of neurological decline, especially ataxia and dementia. Previously, we characterized three pedigrees of individuals with PME and ataxia, where either clinical features or linkage mapping excluded known PME loci. This report identifies a mutation in PRICKLE1 (also known as RILP for REST/NRSF interacting LIM domain protein) in all three of these pedigrees. The identified PRICKLE1 mutation blocks the PRICKLE1 and REST interaction in vitro and disrupts the normal function of PRICKLE1 in an in vivo zebrafish overexpression system. PRICKLE1 is expressed in brain regions implicated in epilepsy and ataxia in mice and humans, and, to our knowledge, is the first molecule in the noncanonical WNT signaling pathway to be directly implicated in human epilepsy.

Public knowledge and attitudes towards epilepsy in Jordan.

BACKGROUND: Social acceptances of people with epilepsy very often constitute a considerable problem for patients and their family. Nationwide opinion polls on the public knowledge and attitudes towards epilepsy have been reported from several countries. The purpose of this study is to assess the knowledge and attitudes of the Jordanian public towards epilepsy, which have not been verified before. METHODS: A total of 16,044 people (8158 males and 7886 females) living in different areas of Jordan were interviewed by invitation using standard four set questionnaire constructed from previous similar studies (Caveness and Gallup) that tested public knowledge and attitudes toward epilepsy. Two hundred and thirty senior students of the faculty of pharmacy at Jordan University of Science and Technology are involved in this study. Each student interviewed at least 50 individuals, aged 18 years or older, from their immediate community including family members, relatives, neighbors and friends by invitation. The interviews took place during the period from February to June of 2005. RESULTS: Eighty-eight percent had read or knew about epilepsy, and 52.4% had witnessed an epileptic attack at least once in their life. From the people interviewed, 84.7% believed that the cause of epilepsy is a neurological disease, and 80.6% believe that the main symptom is brief loss of consciousness. The response of the younger participants and those with higher education were statistically significant more positive regarding the knowledge on causes and symptoms of epilepsy. More than 70% accepts shaking hands with people with epilepsy; they also believe that people with epilepsy are able to have children and to get high academic degrees. Less than 50% accepts letting their children play with children with epilepsy or employ people with epilepsy. Nine percent had negative attitudes, and believed that patients with epilepsy are insane and 88.5% objects the marriage of people with epilepsy to their sons or daughters. Approximately one third of the respondents believed that epilepsy is more dangerous than diabetes mellitus and hypertension. CONCLUSIONS: The overall knowledge and attitudes of Jordanians towards epilepsy is relatively comparable with the results from Asian countries but more negative when compared with reports from the Western countries. Consequently, well-organized educational campaigns are needed to improve public perception about epilepsy.

A distinct autosomal recessive ataxia maps to chromosome 12 in an inbred family from Jordan.

Autosomal recessive ataxias are a heterogeneous group of rare disorders characterized by early onset ataxia associated with neurologic, ophthalmologic or systemic signs. The ataxias associated with myoclonus, epilepsy and progressive neurological degeneration are usually included with the progressive myoclonus epilepsies, one of which is Unverricht-Lundborg disease. We identified four siblings with ataxia, juvenile onset progressive action tremor and atonic seizures from a Jordanian family. The mode of inheritance of this syndrome is autosomal recessive. We performed a genome-wide screen for linkage and fine mapped the region that contains the disease locus. The four affected siblings have ataxia noted at the onset of walking with dysarthria and bulbar features, but no cerebellar hypoplasia on MRI. They all developed a fine tremor that progressed to a coarse action tremor, as well as atonic seizures. Treatment with valproate fully controlled the seizures and improved the tremor, but did not change the course of the ataxia. We mapped the gene responsible for this disorder to the pericentromeric region of chromosome 12. A recently described autosomal recessive variant of Unverricht-Lundborg disease also maps to the same region. We discuss the similarities and differences between our family and the family with the Unverricht-Lundborg disease variant.

Effects of long-term use Topiramate on fertility and growth parameter in adult male rats.

PURPOSE: A case control study was conducted to assess the effects of long-term ingestion of Topiramate on fertility, body and reproductive organ weight and level of sex hormones in Sprague-Dawley male rats. METHODS: Ten adult male rats were exposed to Topiramate diets at a concentration of 100 mg /kg for 60 days. Another ten control male rats received vehicle (distilled water). After 24 hours of the last dose, animals were autopsied under light anesthesia. Several parameters including, body and reproductive organ weight, sperm count and motility, serum testosterone, FSH, levels of cholesterol, triglyceride, SGOT and SGPT were all measured. Assessment of pregnancies in females mixed with tested males was also measured. The results of histological, histometrical and biochemical profiles were compared to that of the control group, and the significance of these results was measured using student's ''t'' and Chi- square tests. RESULTS: Long-term ingestion of Topiramate for 60 days caused a significant decrease in spermatogenesis in seminiferous tubules of the testes. Sperm motility and density were also significantly reduced in cauda epididymides and testes of the treated group. The body weights and weight of reproductive organs (testes, epididymides, ventral prostate and seminal vesicle) were decreased considerably. Hormonal assay also showed significant decrease in testosterone levels. Testicular cell population dynamics also demonstrated a decrease in the number of both primary and secondary spermatocytes and spermatids in the treatment group. The number of female rats impregnated by male rats on long-term Topiramate diet had decreased. The number of implantations and the number of viable fetuses were also notably decreased in female rats impregnated by male rats ingested Topiramate. Histometry of reproductive organs confirmed these results. CONCLUSION: these results confirm that the long-term Topiramate ingestion produces adverse effects on fertility and reproductive system in adult male rat.

New antiepileptic drugs. A clinical overview.

After a gap of approximately 20 years, a new generation of antiepileptic drugs (AEDs) has recently been developed. More than 8 drugs have been licensed in at least one country during the 1990s. While lamotrigine, gabapentin, vigabatrin and oxcarbazepine are widely used in some countries, felbamate, topiramate, tiagabine, levetiracetam, and zonisamide are still used on a narrow scale. A feeling of optimism occurs after the development of these drugs, although only a small number of epileptic patients become free of seizures after the addition of these new AEDs to their regimen. Generally, the safety profile of the new AEDs is only slightly better than that of established drugs and their efficacy is strongly associated with the use of high doses. This article reviews new AEDs by studying their clinical pharmacological effects, mechanisms of action as antiepileptic agents, side effects, drug-drug interactions and the appropriate regimen of their use.

Guanosine 3`,5`-monophosphate is not a marker of the proepileptic activity of valproic acid in hippocampal brain tissues.

OBJECTIVE: Guanosine 3`,5` monophosphate (cGMP) can be used as a marker of the epileptogenicity of proconvulsant drugs. As valproic acid (VPA), at certain concentrations, acts as a proconvulsant agent in hippocampal pyramidal neurons when tested in the veratridine model, this investigation was conducted to study the effect of proconvulsant concentrations of VPA on the basal level of cGMP in hippocampal tissue. METHODS: Experiments were performed using standard radioimmuonassay techniques in hippocampal tissues from rats. This study was carried out at the Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, Texas, United States of America between 1996-1997. RESULTS: We found that veratridine (0.3, 1 and 2 uM, n=3) increased the level of cGMP in hippocampal tissue in a concentration dependent manner. However, VPA at proepileptic concentrations (0.1, 2, 5 uM, n=3), did not significantly affect the basal level of cGMP when added alone or with veratridine (0.3 uM). CONCLUSION: Guanosine 3`,5` monophosphate is not a marker of the proepileptic activity of VPA in brain tissues.

Iron status: a possible risk factor for the first febrile seizure.

PURPOSE: We conducted a controlled study to investigate the relation of iron status and first febrile seizure (FFS). METHODS: Measures of iron sufficiency including hemoglobin concentration (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and plasma ferritin (PF) were prospectively measured in 75 children with FFS and compared with 75 controls matched for age and sex with febrile illnesses without convulsions. RESULTS: Mean ferritin level was significantly lower in cases with FFS (29.5 +/- 21.3 microg/L) than in controls (53.3 +/- 37.6 microg/L) with p = 0.0001. The proportion of subjects with a PF level