Neurogenic Lower Urinary Tract Dysfunction in Spinal Dysraphism: Morphological and Molecular Evidence in Children

Abstract

Spinal dysraphism, most commonly myelomeningocele, is the typical cause of a neurogenic lower urinary tract dysfunction (NLUTD) in childhood. The structural changes in the bladder wall in spinal dysraphism already occur in the fetal period and affect all bladder wall compartments. The progressive decrease in smooth muscle and the gradual increase in fibrosis in the detrusor, the impairment of the barrier function of the urothelium, and the global decrease in nerve density, lead to severe functional impairment characterized by reduced compliance and increased elastic modulus. Children present a particular challenge, as their diseases and capabilities evolve with age. An increased understanding of the signaling pathways involved in lower urinary tract development and function could also fill an important knowledge gap at the interface between basic science and clinical implications, leading to new opportunities for prenatal screening, diagnosis, and therapy. In this review, we aim to summarize the evidence on structural, functional, and molecular changes in the NLUTD bladder in children with spinal dysraphism and discuss possible strategies for improved management and for the development of new therapeutic approaches for affected children.

The association of urinary BDNF, ATP, and MMP‐2 with bladder compliance in children with myelodysplasia

“…An upregulation of TIMPs is known to cause fibrosis by increased deposition of collagens to the bladder wall, along with an increase in interstitial cells including fibroblasts and myofibroblasts 20 . The loss of smooth muscle in the bladder tissues of children with myelodysplasia is compensated by the formation of type 3 collagen 21 . This situation causes deterioration of type 1/3 collagen ratio, storage of collagen in the extracellular matrix and increase in fibrosis.…”

“…3 collagen. 21 This situation causes deterioration of type 1/ 3 collagen ratio, storage of collagen in the extracellular matrix and increase in fibrosis. This process results in decreased bladder compliance, increased intravesical pressure and long-term renal injury.…”

Folic acid supplementation rescues bladder injury in fetal rats with myelomeningocele

“…Neurogenic bladder (NB) is a complicated condition that has historically been a leading source of morbidity and mortality in children with myelomeningocele (MMC) (Planta et al, 2023). Clinical MMC with urinary tract dysfunction has a negative impact on their quality of life as well as their social and occupational abilities (Smith, 1972).…”