Epilepsy, speech delay, and mental retardation in facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies which is related to the deletion of tandem repeats on chromosome 4q35. Extramuscular features such as hearing loss, retinopathy, mental retardation, and epilepsy, may be observed in patients carrying large 4q35 deletions resulting in fragment sizes less than 12 kilobases (kb) (normal >35 kb). We report on a family affected by FSHD carrying a small 4q35 deletion and residual fragments length of 17 kb, presenting with epilepsy (three patients), speech delay (two), and mental retardation (one). In all patients semeiology of seizures and interictal EEG anomalies were congruent with a localization-related epilepsy possibly involving the temporal lobe.In conclusion, we provide further evidences that extramuscular findings such as epilepsy, speech delay, and mental retardation may occur in those patients carrying smaller 4q35 deletions, suggesting that a close correlation between 4q35 fragment size and clinical severity in FSHD is therefore not constant. Moreover, a review of the literature and our observations seem to suggest that focal epilepsies, likely related to the temporal lobe in the present family, represent the main type of epilepsy occurring in children with FSHD.     

Growth and development of children conceived by in-vitro maturation of human oocytes

AIMS: The objective of this study is to evaluate the physical and mental development of infants born on in-vitro maturation (IVM) programs. STUDY DESIGN: We compare 21 IVM children as study group and 21 non-IVM children as control group. We performed a general physical examination for malformations, neurological examination, developmental examination (Bayley Scales) on the IVM group and the non-IVM group. RESULTS: We found all the children with normal karyotype and without major malformation in both IVM and non-IVM groups. The mean Mental Development Index scores for IVM subjects and the comparison group were 92.71+/-10.47 and 97.19+/-8.88, respectively (p=0.074). The mean Psychomotor Development Index scores were 96.67+/-8.91 and 96.19+/-7.05, respectively (p=0.817). CONCLUSIONS: This is the first study designed to evaluate the physical growth and developmental indices of IVM children with combinational priming protocol of FSH and hCG. Our results suggest that IVM children didn't show developmental delay during infancy and early childhood.     

Effects of calcium channel inhibitors on ethanol effects and pharmacokinetics in healthy volunteers

Previous studies have shown that calcium channel antagonists alter the effects of alcohol in animals and humans. We selected a phenylalkylamine, verapamil, and a dihydropyridine, nimodipine, to determine whether these drugs would affect the subjective or psychomotor effects of ethanol in humans. Subjects ingested verapamil (80 mg, PO), nimodipine (30 and 60 mg, PO), or placebo 60 min before drinking an alcohol (0.7 g/kg) or placebo beverage. Subjects' mood, psychomotor performance, physiological status, and blood alcohol levels were assessed up to 3 h after beverage ingestion. Alcohol increased “drunk” ratings and impaired psychomotor performance (p < 0.05). Blood alcohol levels were decreased by nimodipine pretreatment, but not by verapamil pretreatment. Subjective and psychomotor effects of alcohol were not altered as a function of nimodipine or verapamil pretreatment. Nimodipine, verapamil, and alcohol, either alone or in combination, had no effect on blood pressure or heart rate.     

RETRACTED ARTICLE: Perinatal and first year outcomes of spontaneous versus assisted twins: a single center experience

OBJECTIVE: The aim is to compare naturally conceived twins with twins conceived by assisted reproductive techniques (ART) by means of perinatal outcome, behavioural patterns and psychomotor development. MATERIAL AND METHODS: Three hundred and five spontaneous and 119 assisted twins were compared in aspects of behavioural patterns, mental and psychomotor development, as well as maternal and gestational age, foetal presentation, birth weight, sex, Apgar scores, perinatal complications, delivery route, and admission to neonatal intensive care unit (NICU) RESULTS: Although the maternal age was higher in assisted twins, the mean gestational age and birth weight of assisted twins were significantly less than those of spontaneous twins. The assisted twins did not differ from the naturally conceived twins in aspects of presentation, Apgar scores, admission to NICU and perinatal complications. However, caesarean section rate and the delivery rate of male foetuses were significantly higher in assisted twins. During the first year of life, retardation in mental and psychomotor development was more pronounced in assisted twins. Also assisted twins experienced behavioural problems and difficulties in parent-child interactions more frequently. CONCLUSIONS: Although twins born to assisted pregnancies had significantly shorter duration of gestation and thus less birth weight, their perinatal outcome was similar to that of spontaneous twins. The mothers of assisted twins may be keener on getting intensive prenatal care, which might in turn help to diminish any possible maternal and foetal risks. However, assisted twins showed significantly retarded psychomotor and mental development and experienced problems with environmental factors more frequently during their first year.     

General anesthesia for cesarean delivery and childhood neurodevelopmental and perinatal outcomes: a secondary analysis of a randomized controlled trial

BackgroundIn 2016, the U.S. Food and Drug Administration expressed concern that neurodevelopment may be negatively affected by anesthesia or sedation exposure in pregnancy or before three years of age. We examined the association between general anesthesia at the time of cesarean delivery and early childhood neurodevelopment.MethodsA secondary analysis of a multicenter randomized controlled trial assessing magnesium for prevention of cerebral palsy in infants at risk for preterm delivery. Exposure was general compared to neuraxial anesthesia. The primary outcome was motor or mental delay at two years of age, assessed by Bayley Scales of Infant Development II (BSIDII). Secondary outcomes included BSIDII subdomains and perinatal outcomes. Multivariable logistic regression models were performed to control for confounders.ResultsOf 557 women undergoing cesarean delivery, 119 (21%) received general anesthesia. There were no differences in the primary composite outcome of developmental delay (aOR 0.93, 95% CI 0.61 to 1.43) or the BSIDII subdomains of mild, moderate, or severe mental delay, or mild or moderate motor delay. Severe motor delay was more common among infants exposed to general anesthesia (aOR 1.98, 95% CI 1.06 to 3.69). Infants exposed to general anesthesia had longer neonatal intensive care stays (51 vs 37 days, P=0.010).ConclusionsGeneral anesthesia for cesarean delivery was not associated with overall neurodevelopmental delay at two years of age, except for greater odds of severe motor delay. Future studies should evaluate this finding, as well as the impact on neurodevelopment of longer or multiple anesthetic exposures across all gestational ages.     

Transient amelioration of the sensitization of cocaine-induced behaviors in rats by the induction of tolerance

Intermittent administration of cocaine produced a progressive increase in the stereotypy response of rats to a challenge dose of cocaine (7.5 mg/kg, i.p.). Continuous infusion of cocaine (80 mg/kg per day) via osmotic pumps for 7 days into the sensitized rats produced tolerance to the behavioral responses to the challenge dose of cocaine 1 day after the removal of the pumps. Therefore, tolerance can mask the expression of behavioral sensitization in rats. However, by 10 days after the removal of the pumps, the behavioral tolerance was reversed and the rats again displayed a sensitized response to cocaine. Therefore, the tolerance to cocaine was temporary while the underlying sensitization persisted. The development of tolerance did not alter the underlying sensitization demonstrating that these represent independent phenomena. The relationship between sensitization and tolerance observed in these studies may provide a model relevant to the progress in humans of addiction to psychomotor stimulants.     

Behavioral effects of cocaine alone and in combination with selective dopamine antagonists in the squirrel monkey

Effects of cocaine, alone and in combination with the dopaminergic antagonists, SCH 23390 and haloperidol were studied in squirrel monkeys trained to respond under fixed-interval schedules of electric-shock presentation. Cocaine at intermediate doses (0.1 and 0.3 mg/kg) increased rates of responding under the fixed-interval schedule and during 1-min timeout periods that separated each fixed-interval component. Higher doses (1.0–3.0 mg/kg) decreased response rates. Cocaine also dose-dependently altered the temporal pattern of responding characteristic of behavior under fixed-interval schedules. Haloperidol (0.003–0.1 mg/kg) and SCH 23390 (0.001–0.03 mg/kg) dose-dependently decreased rates of responding. A low dose (0.001 mg/kg) of the selective D1 antagonist, SCH 23390, did not appreciably alter the effects of cocaine. Higher doses (0.003–0.01 mg/kg), which when given alone decreased rates of responding, attenuated the increases in response rates produced by cocaine. In addition, the decreases in response rates produced by the higher dose of cocaine were attenuated by 0.01 mg/kg SCH 23390. The alterations in temporal patterning of responding under the fixed-interval schedule were not antagonized by any dose of SCH 23390. Haloperidol (0.003 mg/kg) did not appreciably alter the effects of cocaine; higher doses (0.01–0.03 mg/kg), which when given alone decreased rates of responding, attenuated the increases in response rates produced by 0.1 mg/kg cocaine. The decreases in response rates under the fixed-interval schedule that were produced by higher doses, or the changes in temporal patterning of responding at any dose of cocaine, were not antagonized by any dose of haloperidol that was studied. The present results suggest that the effects of cocaine on schedule-controlled behavior in squirrel monkeys are not the exclusive domain of one dopamine receptor subtype.