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.

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.

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.

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