Pregabalin Add-On vs. Dose Increase in Levetiracetam Add-On Treatment: A Real-Life Trial in Dogs With Drug-Resistant Epilepsy

Epilepsy is a common neurological disorder affecting 0.6–0.75% of dogs in veterinary practice. Treatment is frequently complicated by the occurrence of drug-resistant epilepsy and cluster seizures in dogs with idiopathic epilepsy. Only few studies are available to guide treatment choices beyond licensed veterinary drugs. The aim of the study was to compare antiseizure efficacy and tolerability of two add-on treatment strategies in dogs with drug-resistant idiopathic epilepsy. The study design was a prospective, open-label, non-blinded, comparative treatment trial. Treatment success was defined as a 3-fold extension of the longest baseline interseizure interval and to a minimum of 3 months. To avoid prolonged adherence to a presumably ineffective treatment strategy, dog owners could leave the study after the third day with generalized seizures if the interseizure interval failed to show a relevant increase. Twenty-six dogs (mean age 5.5 years, mean seizure frequency 4/month) with drug-resistant idiopathic epilepsy and a history of cluster seizures were included. Dogs received either add-on treatment with pregabalin (PGB) 4 mg/kg twice daily (14 dogs) or a dose increase in levetiracetam (LEV) add-on treatment (12 dogs). Thirteen dogs in the PGB group had drug levels within the therapeutic range for humans. Two dogs in the PGB group (14.3%; 2/14) and one dog in the LEV group (8.3%; 1/12) achieved treatment success with long seizure-free intervals from 122 to 219 days but then relapsed to their early seizure frequency 10 months after the study inclusion. The overall low success rates with both treatment strategies likely reflect a real-life situation in canine drug-resistant idiopathic epilepsy in everyday veterinary practice. These results delineate the need for research on better pharmacologic and non-pharmacologic treatment strategies in dogs with drug-resistant epilepsy

Spider Silk Constructs Enhance Axonal Regeneration and Remyelination in Long Nerve Defects in Sheep

BACKGROUND: Surgical reapposition of peripheral nerve results in some axonal regeneration and functional recovery, but the clinical outcome in long distance nerve defects is disappointing and research continues to utilize further interventional approaches to optimize functional recovery. We describe the use of nerve constructs consisting of decellularized vein grafts filled with spider silk fibers as a guiding material to bridge a 6.0 cm tibial nerve defect in adult sheep. METHODOLOGY/PRINCIPAL FINDINGS: The nerve constructs were compared to autologous nerve grafts. Regeneration was evaluated for clinical, electrophysiological and histological outcome. Electrophysiological recordings were obtained at 6 months and 10 months post surgery in each group. Ten months later, the nerves were removed and prepared for immunostaining, electrophysiological and electron microscopy. Immunostaining for sodium channel (NaV 1.6) was used to define nodes of Ranvier on regenerated axons in combination with anti-S100 and neurofilament. Anti-S100 was used to identify Schwann cells. Axons regenerated through the constructs and were myelinated indicating migration of Schwann cells into the constructs. Nodes of Ranvier between myelin segments were observed and identified by intense sodium channel (NaV 1.6) staining on the regenerated axons. There was no significant difference in electrophysiological results between control autologous experimental and construct implantation indicating that our construct are an effective alternative to autologous nerve transplantation. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that spider silk enhances Schwann cell migration, axonal regrowth and remyelination including electrophysiological recovery in a long-distance peripheral nerve gap model resulting in functional recovery. This improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery

Illustrationen als Paratext beim Ubersetzen : Mit Beispielen aus einem Werk von O. Preusler

Purpose: The authors tested associations between (a) parent-reported temporary vs. persistent vocabulary delay and (b) parent-reported behavioral/emotional problems in a sample of 5,497 young Dutch children participating in a prospective population-based study. Method: Mothers completed the MacArthur Communicative Development Inventory-Netherlands (Zink & Lejaegere, 2003) at age 18 months and the Language Development Survey (Rescorla, 1989) at age 30 months, with expressive vocabulary delay defined as scores in the lowest 15th age-and gender-specific percentiles. The Child Behavior Checklist (Achenbach & Rescorla, 2000) was completed by mothers when their children were age 18 months and by both parents when their children were age 36 months, from which Internalizing Problems and Externalizing Problems scores were analyzed. Results: All analyses were adjusted for covariates. Expressive vocabulary delay at age 18 months was weakly related to Internalizing Problems scores at age 18 months as well as mother-reported Externalizing and Internalizing Problems scores at age 36 months (the latter for boys only). Expressive vocabulary delay at age 30 months was weakly associated with mother-reported Externalizing and Internalizing Problems scores (the latter for boys only) and father-reported Internalizing Problems scores. Persistent expressive vocabulary delay predicted the highest risk of mother-reported internalizing and externalizing problems at age 36 months. Conclusion: This population-based study showed modest associations between vocabulary delay and behavioral/emotional problems detectable from 18 months onward

Diurnal cortisol rhythm and cognitive functioning in toddlers: The Generation R Study

Little is known about the relationship between diurnal cortisol secretion patterns and cognitive function early in life. This population-based study examined whether diurnal cortisol rhythms and cognitive functioning in toddlers are related. Within the Generation R Study, parents of 364 infants (median age: 14.2 months) collected saliva samples at five moments during one day. We assessed the diurnal cortisol rhythm by calculating the area under the curve (AUC), the cortisol awakening response (CAR), and the diurnal slope. Verbal cognitive functioning and fine motor development was determined at age 18 months. Nonverbal cognitive functioning was assessed at age 30 months. A more positive CAR was associated with a lower risk of delay in language comprehension (OR per 1-SD CAR: 0.62, 95%CI: 0.40-0.98, p =.04), a lower risk of nonoptimal fine motor development (OR per 1-SD slope: 0.74, 95%CI: 0.57-0.96, p =.03), and a lower risk of delay in nonverbal cognitive development (OR per 1-SD CAR: 0.58, 95%CI: 0.38-0.90, p =.02). Also, children with flatter slopes had a lower risk of delay in nonverbal cognitive development (OR per 1-SD slope: 0.51, 95%CI: 0.34-0.76, p =.001). Higher AUC levels were associated with a higher risk of delay in language production. These results show that variations in diurnal cortisol rhythms are already associated with variations in cognitive functioning at a young age. Infants with a diurnal cortisol pattern indicative of less stress and more cortisol reactivity, that is, lower AUC levels and a more positive CAR, show a lower risk of delay in cognitive functioning as toddlers

Parental family stress during pregnancy and cognitive functioning in early childhood: The Generation R Study

We investigated whether parental family stress during pregnancy is associated with cognitive functioning in early childhood in a population-based cohort (n= 3139). Family stress was assessed using the Family Assessment Device at the 20th week of pregnancy and was reported by mothers and fathers. Mothers completed the MacArthur Communicative Development Inventory, measuring children's verbal cognitive functioning, when children were 18 months and they completed the Parent Report of Children's Abilities, measuring nonverbal cognitive functioning, when children were 2 years old. Maternal prenatal family stress was related to children's low word comprehension and poorer nonverbal cognitive development independent of paternal reports. In a subset of 639 children, maternal prenatal family stress was also associated with observational assessments of poor effortful control at age 37 months. Paternal prenatal family stress was only related to poorer nonverbal cognitive development, independent of the mother. When both parents had high levels of prenatal family stress, children displayed particularly poor nonverbal cognitive development. These findings emphasize the significance of parental prenatal family stress for child developmental outcomes

Fetal growth from mid- to late pregnancy is associated with infant development: the Generation R Study

Aim The aim of this study was to investigate within a population-based cohort of 4384 infants (2182 males, 2202 females) whether fetal growth from early pregnancy onwards is related to infant development and whether this potential relationship is independent of postnatal growth. Method Ultrasound measurements were performed in early, mid-, and late pregnancy. Estimated fetal weight was calculated using head and abdominal circumference and femur length. Infant development was measured with the Minnesota Infant Development Inventory at 12 months (SD 1.1mo, range 10-17mo). Information on postnatal head size and body weight at 7 months was obtained from medical records. Results After adjusting for potential confounders and for postnatal growth, faster fetal weight gain from mid- to late pregnancy predicted a reduced risk of delayed social development (odds ratio [OR] 0.82; 95% confidence interval [CI] 0.71-0.95, p=0.008), self-help abilities (OR 0.84; 95% CI 0.73-0.98, p=0.023), and overall infant development (OR 0.65; 95% CI 0.49-0.87, p=0.003). Similar findings were observed for fetal head growth from mid- to late pregnancy. Interpretation Faster fetal growth predicts a lower risk of delayed infant development independent of postnatal growth. These results suggest that reduced fetal growth between mid- and late pregnancy may determine subsequent developmental outcomes

Electrophysiological recordings of spider silk constructs and autologous nerve transfer.

<p>(A) EDxNCV: Box plot diagram of the in vivo measurement of the motor nerve conduction velocity (mNCV) at time point T1 (after 6 months post surgery) and at time point T2 (after 10 months post surgery). ⊤ =  maximum, ⊥ =  minimum, — =  median, □ = mean. A box includes 50% of the values. P values of Mann–Whitney–Wilcoxon-test for paired samples are indicated in the figure. Values of P≤0.05 were considered significant. (B) EDxAMP: Box plot diagram of the in vivo measurement of the compound muscle action potential amplitudes at time point T1 and at time point T2. ⊤ =  maximum, ⊥ =  minimum, — =  median, □ = mean. A box includes 50% of the values. P values of Mann–Whitney–Wilcoxon-test for paired samples are indicated in the figure. Values of P≤0.05 were considered significant.</p