Long-term biopsychosocial issues and health-related quality of life in young adolescents and adults treated for childhood Complex Regional Pain Syndrome, type 1.

OBJECTIVES: Treatment for childhood Complex Regional Pain Syndrome (CRPS) is associated with long-term recovery. The present study aimed to investigate the long-term biopsychosocial status and quality of life in young adolescents and adults after the treatment of childhood CRPS. METHODS: A 4 year follow-up of individuals with childhood-CRPS, type 1 (n=22; age:12 years (years) [median] at treatment and 17 years at follow-up) was completed. Biopsychosocial status and quality of life were assessed with structured interviews, using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), the Strengths and Difficulties Questionnaire (SDQ), the Pediatric Pain Coping Inventory (PPCI), and the Pediatric Quality of Life Inventory (PedsQL). Comparisons were made with normative samples of age-matched controls. RESULTS: CRPS at follow-up was still present in seven out of 22, and non-CRPS pain symptoms were found in 12 out of 22 individuals. Signs of mental health pain-related problems, including phobias and obsessive-compulsive disorder, were observed in ten out of 19 individuals. Mental well-being, social functioning, and quality of life (SDQ and PedsQL) were independent of pain status (p>0.05). Adaptive pain coping strategies were utilized regardless of pain status (PPCI). Social functioning (p<0.01) and the quality of life (p=0.01) were attenuated and statistically significantly poorer than healthy age-matched young adults but better than for fibromyalgia subjects. CONCLUSIONS: A subset of individuals treated for childhood-CRPS, type 1 experiences long-term consequences of persistent pain, a decrease in quality of life indicators, and demonstrates significant psychosocial issues. Childhood-CRPS is suggested to be associated with long-term psychosocial consequences and poorer quality of life than found in age-related healthy peers. Subjects treated for childhood CRPS may need a longer clinical follow-up attempting to preclude relapse of CRPS and non-CRPS pain.

PDGF-B Is Required for Development of the Glymphatic System.

The glymphatic system is a highly polarized cerebrospinal fluid (CSF) transport system that facilitates the clearance of neurotoxic molecules through a brain-wide network of perivascular pathways. Herein we have mapped the development of the glymphatic system in mice. Perivascular CSF transport first emerges in hippocampus in newborn mice, and a mature glymphatic system is established in the cortex at 2 weeks of age. Formation of astrocytic endfeet and polarized expression of aquaporin 4 (AQP4) consistently coincided with the appearance of perivascular CSF transport. Deficiency of platelet-derived growth factor B (PDGF-B) function in the PDGF retention motif knockout mouse line Pdgfbret/ret suppressed the development of the glymphatic system, whose functions remained suppressed in adulthood compared with wild-type mice. These experiments map the natural development of the glymphatic system in mice and define a critical role of PDGF-B in the development of perivascular CSF transport.

The Glymphatic System: A Beginner's Guide.

The glymphatic system is a recently discovered macroscopic waste clearance system that utilizes a unique system of perivascular tunnels, formed by astroglial cells, to promote efficient elimination of soluble proteins and metabolites from the central nervous system. Besides waste elimination, the glymphatic system also facilitates  brain-wide distribution of several compounds, including glucose, lipids, amino acids, growth factors, and neuromodulators. Intriguingly, the glymphatic system function mainly during sleep and is largely disengaged during wakefulness. The biological need for sleep across all species may therefore reflect that the brain must enter a state of activity that enables elimination of potentially neurotoxic waste products, including ß-amyloid. Since the concept of the glymphatic system is relatively new, we will here review its basic structural elements, organization, regulation, and functions. We will also discuss recent studies indicating that glymphatic function is suppressed in various diseases and that failure of glymphatic function in turn might contribute to pathology in neurodegenerative disorders, traumatic brain injury and stroke.