In humans, tobacco withdrawal produces symptoms that contribute to the difficulty associated with smoking cessation. Nicotine withdrawal symptoms can also be observed in rodents. A major standing question is which nicotinic receptor subtypes and which areas of the brain are necessary for nicotine withdrawal to occur. Using knock-out mice, we previously showed that the β4, but not the β2 subunit of nicotinic acetylcholine receptors, is necessary for the somatic manifestations of nicotine withdrawal. Since the β4 subunit is highly expressed in the medial habenula, we focused our studies on the medial habenula and its primary target, the interpeduncular nucleus. In particular, we studied nicotine withdrawal in mice lacking the α2 or the α5 nicotinic receptor subunits, which are highly expressed in the interpeduncular nucleus. We precipitated withdrawal by systemically injecting the nicotinic antagonist mecamylamine in mice chronically treated with nicotine. Both the α2 and the α5 null mutations abolished the somatic manifestations of nicotine withdrawal. In addition, in wild-type mice chronically treated with nicotine, mecamylamine precipitated withdrawal when microinjected into the habenula or the interpeduncular nucleus, but not into the cortex, ventral tegmental area or hippocampus. Our results demonstrate a major role for the habenulo-interpeduncular system and the nicotinic receptor subunits expressed therein, in nicotine withdrawal symptoms. Our data suggest that the efforts to develop new smoking cessation therapies should concentrate on these areas and receptor types.

Neurogenic bladder is a heterogeneous entity that may result from a variety of conditions affecting the central or peripheral nervous systems. Regardless of etiology, the overall goals of management are primarily twofold. As a neurogenic bladder may affect the ability to store urine safely and to empty the bladder efficiently, early management is focused on optimization of bladder storage function to prevent irreversible injury to either the upper or lower urinary tracts. In older children, this goal is added to the challenge of maximizing quality of life through achievement of urinary continence and independence in bladder management that continues into the transition to adulthood. In this review, we seek to bring the reader up-to-date regarding management of the pediatric neurogenic bladder with a focus on literature published in the past year. We discuss key contributions related to fetal intervention for myelomeningocele, monitoring and medical management of the neurogenic bladder and prediction of postoperative outcomes. Put together, these studies highlight the continued need for further research to improve evidence-based medical and surgical decision-making strategies for children affected by neurogenic bladder.

Children with bladder dysfunction resulting in increased storage pressure are at risk for renal deterioration. The current gold standard for evaluation of bladder pressure is urodynamics, an invasive test requiring catheterization. We evaluated ultrasound shear wave elastography as a novel means of assessing bladder biomechanical properties associated with increased bladder pressure. Concurrent shear wave elastography and urodynamics were performed. Ultrasound shear wave elastography images were obtained of the anterior and posterior wall when empty and at 25%, 50%, 75% and 100% expected bladder capacity, and end fill volume. Regions of interest were confirmed by a pediatric radiologist. Bladder cohorts were defined as compliant (capacity detrusor pressure less than 25 cm H2O) and noncompliant (25 cm H2O or greater). Pearson correlation coefficients and a mixed effects model evaluated the relationship between shear wave speed and detrusor pressure, compliance and normalized compliance. An unpaired t-test was used for between cohort analyses. In all 23 subjects mean shear wave speed of the anterior and posterior bladder walls significantly correlated with detrusor pressure throughout filling. When comparing compliant and noncompliant bladders, mean shear wave speed and detrusor shear wave speed of the anterior wall significantly increased with filling of noncompliant bladders. Shear wave speed remained at baseline levels in compliant bladders. Mean shear wave speed of the anterior wall was significantly correlated with compliance and normalized compliance. Ultrasound shear wave elastography bladder measurements correlate well with bladder storage pressure, and shear wave speed measurements differ between compliant and noncompliant bladders. This is the first known study to demonstrate that shear wave elastography is promising as a bedside modality for the assessment of bladder dysfunction in children.