Ventral striatum and stuttering: Robust evidence from a case-control study applying DARTEL.

A prominent theory of developmental stuttering highlights (dys-)function of the basal ganglia (and in particular the ventral striatum) as a main neural mechanism behind this speech disorder. Although the theory is intriguing, studies on gray matter volume differences in the basal ganglia between people who stutter and control persons have reported heterogeneous findings, either showing more or less gray matter volume of the aforementioned brain structure across the brain's hemispheres. Moreover, some studies did not observe any differences at all. From today's perspective several of the earlier studies are rather underpowered and also used less powerful statistical approaches to investigate differences in brain structure between people who stutter and controls. Therefore, the present study contrasted a comparably larger sample of n = 36 people who stutter with n = 34 control persons and applied the state of the art DARTEL algorithm (Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra) to analyze the available brain data. In the present data set stuttering was associated with higher gray matter volume of the right caudate and putamen region of the basal ganglia in patients. Our observation strongly supports a recent finding reporting a larger nucleus accumbens in the right hemisphere in people who stutter when compared to control persons. The present findings are discussed in the context of both compensatory effects of the brain and putative therapeutic effects due to treatment of stuttering.

Mepolizumab-a novel option for the treatment of hypereosinophilic syndrome in childhood.

BACKGROUND: Mepolizumab was originally intended as a therapeutic agent for atopic asthma in adults, and consequently, little is known about its use in children. Up to now, corticosteroids have formed the basis of the initial treatment of hypereosinophilic syndromes and are shown to be effective in most patients. To analyze the effect of mepolizumab in children is the aim of this study. METHODS: We are reporting the experience of the effect of mepolizumab in 2 pediatric patients with hypereosinophilic syndrome that was not sufficiently controlled by other drugs. In addition, the literature regarding the treatment with mepolizumab in pediatric and adult patients is reviewed for the most important studies regarding safety and efficacy. RESULTS: Mepolizumab therapy showed in 2 pediatric patients with severe hypereosinophilic syndrome a safe and efficient therapeutic approach. No significant intolerances appeared. Furthermore, treatment with systemic corticosteroids was terminated, and therefore, severe side effects were avoided in our pediatric cases. CONCLUSIONS: Anti-IL-5 antibodies, which can be applied without substantial drug intolerances, are a new, safe, and effective treatment option for pediatric patients with hypereosinophilic syndrome.

Impaired motor inhibition in adults who stutter - evidence from speech-free stop-signal reaction time tasks.

Idiopathic stuttering is a fluency disorder characterized by impairments during speech production. Deficits in the motor control circuits of the basal ganglia have been implicated in idiopathic stuttering but it is unclear how these impairments relate to the disorder. Previous work has indicated a possible deficiency in motor inhibition in children who stutter. To extend these findings to adults, we designed two experiments to probe executive motor control in people who stutter using manual reaction time tasks that do not rely on speech production. We used two versions of the stop-signal reaction time task, a measure for inhibitory motor control that has been shown to rely on the basal ganglia circuits. We show increased stop-signal reaction times in two independent samples of adults who stutter compared to age- and sex-matched control groups. Additional measures involved simple reaction time measurements and a task-switching task where no group difference was detected. Results indicate a deficiency in inhibitory motor control in people who stutter in a task that does not rely on overt speech production and cannot be explained by general deficits in executive control or speeded motor execution. This finding establishes the stop-signal reaction time as a possible target for future experimental and neuroimaging studies on fluency disorders and is a further step towards unraveling the contribution of motor control deficits to idiopathic stuttering.

Non-verbal sensorimotor timing deficits in children and adolescents who stutter.

There is growing evidence that motor and speech disorders co-occur during development. In the present study, we investigated whether stuttering, a developmental speech disorder, is associated with a predictive timing deficit in childhood and adolescence. By testing sensorimotor synchronization abilities, we aimed to assess whether predictive timing is dysfunctional in young participants who stutter (8-16 years). Twenty German children and adolescents who stutter and 43 non-stuttering participants matched for age and musical training were tested on their ability to synchronize their finger taps with periodic tone sequences and with a musical beat. Forty percent of children and 90% of adolescents who stutter displayed poor synchronization with both metronome and musical stimuli, falling below 2.5% of the estimated population based on the performance of the group without the disorder. Synchronization deficits were characterized by either lower synchronization accuracy or lower consistency or both. Lower accuracy resulted in an over-anticipation of the pacing event in participants who stutter. Moreover, individual profiles revealed that lower consistency was typical of participants that were severely stuttering. These findings support the idea that malfunctioning predictive timing during auditory-motor coupling plays a role in stuttering in children and adolescents.

Risk for late-onset blood-culture proven sepsis in very-low-birth weight infants born small for gestational age: a large multicenter study from the German Neonatal Network.

BACKGROUND: It was the aim of this study to assess whether very-low-birth-weight (VLBW) infants born small for gestational age (SGA; birth weight less than 10th percentile) are at increased risk for late-onset sepsis. METHODS: This was a prospective, multicenter study of the German Neonatal Network including VLBW infants from 23 to < 32 weeks post menstrual age born 2009-2011. Outcomes were compared between VLBW infants born SGA (birth weight less than tenth percentile according to gestational age and gender) and non-SGA infants. The main outcome measure was at least 1 episode of late-onset sepsis defined as blood-culture-confirmed clinical sepsis occurring at ≥ 72 hours of age. RESULTS: 5886 VLBW infants were included. In SGA infants (n = 692), an increased incidence of late-onset sepsis was noted compared with non-SGA infants (20.1% vs. 14.3 %, P < 0.001). This difference was only observed among infants with a gestational age of 27 to < 32 weeks and attributed to sepsis episodes with coagulase-negative staphylococci (12.8% vs. 8.3%, P < 0.001). Different treatment modalities (eg more frequent use of central venous lines) and longer duration of invasive therapies (parenteral nutrition, mechanical ventilation, hospitalization) may account for the increased sepsis risk with coagulase-negative staphylococci in our SGA cohort. In a multivariate logistic regression analysis, higher gestational age [per week; odds ratio (OR): 0.75, 95% confidence interval (CI): 0.72-0.78, P< 0.0001], treatment with antenatal steroids (OR: 0.7, 95% CI: 0.53-0.92, P = 0.01), German descendance (OR: 0.76, 95% CI: 0.63-0.91, P = 0.003) and prophylaxis with glycopeptide antibiotics (OR: 0.64, 95% CI: 0.47-0.87, P = 0.005) were shown to be protective against late-onset sepsis. In contrast, longer duration of parenteral nutrition (per day; OR: 1.016, 95% CI: 1.011-1.021, P < 0.0001) and SGA were found to be risk factors (OR: 1.31, 95% CI: 1.02-1.68, P= 0.03). CONCLUSIONS: SGA contributes to the risk of late-onset sepsis in VLBW infants. Future studies are needed to investigate the underlying pathophysiology to guide individualized preventive measures in this vulnerable subgroup.

Intrauterine growth restriction and the innate immune system in preterm infants of ≤32 weeks gestation.

OBJECTIVE: Intrauterine growth restriction (IUGR) is a well-known cause of adverse neonatal outcomes. As it may have an impact on innate immune responses, we aimed to investigate several parameters of the innate immune response in preterm infants of ≤32 weeks gestation who were small for gestational age (SGA). METHODS: We compared clinical data of SGA (n = 20) and appropriate for gestational age (AGA; n = 124) newborns with a gestational age of ≤32 weeks. We investigated full blood counts at birth and on days 3 and 7 of life and cytokine immune responses in a human whole cord blood assay. RESULTS: SGA preterm infants had a higher risk of the combined outcome mortality or bronchopulmonary dysplasia. Numbers of white blood cells and neutrophils were diminished in SGA infants at birth and on day 3. At birth, platelet counts were also diminished while the number of nucleated red blood cells tended to be elevated in SGA infants. After stimulation of whole blood cell cultures with lipopolysaccharides, the concentrations of interleukin-6 and interleukin-10 were significantly lower in SGA preterm infants compared to AGA infants. CONCLUSIONS: SGA infants differ remarkably from AGA infants in full blood counts and in their ability to mount an immune response. Whether the quantitative deficiency in innate immunity plays a role for adverse outcomes needs to be investigated in larger future trials.