Infants born to mothers with epilepsy are at substantial risk for neurocognitive and behavioral disorders. Although exposure of the child to antiepileptic drugs (AEDs) during pregnancy and postnatally through breast milk has been implicated in disorders of higher cortical function, there have been relatively few clinical or animal studies examining the long-term effects of AEDs on cognition in the developing brain. In the limited animal studies done thus far, drug-specific effects on cognitive function have been identified. Phenobarbital, in particular, has been found to lead to adverse cognitive outcomes, whereas the newer AEDs have generally had more favorable outcomes. Although the pathophysiological mechanisms responsible for these deficits remain largely unknown, there is evidence that AEDs can adversely effect neuronal proliferation and migration, and increase apoptosis. While animal studies can provide valuable information regarding mechanism of AED-induced developmental pathology, they do not provide insight into cortical functions unique to humans, such as speech and language. Understanding the full spectrum of AED-induced effects on the developing brain will require both rigorous basic science and clinical studies.
"all perturbation would break it . Several observations could indeed indicate that network dynamics in the developing neocortex can rapidly switch to a pathological state . Maybe the most striking one is the fact that the neocortex is exceptionally prone to seizures at early developmental stages ( Ben - Ari & Holmes , 2006 ; Bender & Baram , 2007 ; Holmes et al . 2007 ; Scantlebury et al . 2007 ) . For example , it was recently shown that GDPs in that region rapidly evolve towards interictal and ictal - like seizures if synaptic activity levels are pharmacologically increased ( Rheims et al . 2008b ) . Likewise , the blockade of excitatory amino acid transporters ( EAAT ) that remove glutamate from t"
[Show abstract][Hide abstract] ABSTRACT: Several patterns of coherent activity have been described in developing cortical structures, thus providing a general framework for network maturation. A detailed timely description of network patterns at circuit and cell levels is essential for the understanding of pathogenic processes occurring during brain development. Disturbances in the expression timetable of this pattern sequence are very likely to affect network maturation. This review focuses on the maturation of coherent activity patterns in developing neocortical structures. It emphasizes the intrinsic and synaptic cellular properties that are unique to the immature neocortex and, in particular, the critical role played by extracellular glutamate in controlling network excitability and triggering synchronous network waves of activity.
The Journal of Physiology 11/2009; 588(Pt 1):83-91. DOI:10.1113/jphysiol.2009.178798 · 5.04 Impact Factor
"In order to retain statistical power subsequent analyses combined data from both VEP systems, equipment was included as a covariate in the multivariable analyses. Exposure to phenobarbitone has been shown to produce changes in the neonatal brain   and to have an effect on later visual development  and long-term cognition . We conducted sensitivity analyses to test whether inclusion of the 3 infants treated with phenobarbitone contributed to differences in VEP latencies between infants treated pharmacologically for NAS versus those not treated. "
[Show abstract][Hide abstract] ABSTRACT: This study compared the neurological development of 4 month old infants exposed to buprenorphine or methadone during pregnancy to that of a control group of non-exposed infants. Participants were 30 buprenorphine-maintained women, 22 methadone-maintained women and 33 non opioid-dependent controls, and their infants. Women were enrolled during pregnancy as part of an open-label non-randomised flexible-dosing longitudinal study. Groups were matched for maternal age, parity, gravida, and tobacco and alcohol use. Infant neurological development was assessed by measuring latency of pattern reversal visual evoked potentials (VEP). One-way between groups analyses of variance (ANOVA) were conducted to test the statistical significance of differences between the mean latencies of the peak response to two different sized checkerboard patterns (48' and 69' of retinal arc). Infants prenatally exposed to methadone had significantly prolonged latencies, compared with infants in the control group and infants prenatally exposed to buprenorphine, in response to checks of 48' and 69'. VEP latencies of infants prenatally exposed to buprenorphine did not differ significantly from controls for either check size. After adjustment for covariates, prenatal exposure to methadone remained a significant predictor of VEP response to checks of 48', but not 69'. Maternal self-reported used of marijuana during pregnancy made a significant unique contribution to the variance in P1 latencies for both check sizes. Data from this controlled, non-randomised study suggest that buprenorphine may confer an advantage over methadone as a maintenance drug during pregnancy in terms of infant neural development at 4 months of age.
Neurotoxicology and Teratology 09/2009; 32(2):280-8. DOI:10.1016/j.ntt.2009.09.001 · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Zahlreiche tierexperimentelle Untersuchungen zeigen, dass Anästhetika im unreifen Gehirn neurotoxisch wirken können, da sie Apoptose induzieren und die Neuro- sowie Synaptogenese beeinflussen. Im Tierexperiment hat dies erhebliche Auswirkungen auf die neurokognitiven Funktionen der Tiere im späteren Leben. Ob diese tierexperimentellen Ergebnisse auf den Menschen übertragen werden können, ist derzeit Gegenstand intensiver Forschung. In mehreren retrospektiven Untersuchungen konnte kein eindeutiger Zusammenhang zwischen einer Anästhesie im Früh-, Neugeborenen- oder Kleinkindalter und dem Auftreten von Lernstörungen oder Verhaltensauffälligkeiten gefunden werden. Zwei prospektive Studien (GAS und PANDA) sollen weiteren Einblick liefern und diese Frage möglichst klären. Wegen der großen Relevanz des Themas und um für die Problematik im Umgang mit den Eltern mehr Klarheit zu schaffen, haben der Wissenschaftliche Arbeitskreis für Kinderanästhesie und der Wissenschaftliche Arbeitskreis für Neuroanästhesie der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI) auf der Grundlage der derzeitigen Datenlage eine Stellungnahme verfasst ().
Der Anaesthesist 02/2013; 62(2). DOI:10.1007/s00101-013-2139-0 · 0.76 Impact Factor
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