Influencing Factors on Independent Walking in Children With Lumbosacral Lipomas: A Retrospective Cohort Study Based on a 5-Year Untethering Series.

Background: Caregivers are deeply concerned about children achieving independent walking, and evidence-based rehabilitation support is beneficial. However, current research is confined to a single study on spina bifida aperta, leaving a gap in understanding the timing of independent walking for lumbosacral lipomas. Objectives: This study aimed to examine the factors influencing independent walking in children with lumbosacral lipomas. Design: Retrospective cohort study. Methods: This retrospective cohort study included 124 children who underwent untethering surgery for lumbosacral lipomas. The age (in months) at which the children walked independently was used as the primary endpoint, and potential influencing factors, including the type of spinal lipoma, extent of lipoma removal, magnetic resonance imaging features, congenital anomaly complications, urinary/defecation management requirements, foot/toe symptoms, and orthotic device fabrications were analyzed. Results: Multiple logistic regression analysis showed that the most significant influencing factor for delayed independent walking was the presence of systemic combined anomalies (adjusted odds ratio = 15.5, P < .001), while non-systemic malformations, such as suburethral cleft, had limited effects. A subgroup analysis of 94 patients without systemic combined anomalies showed that the presence of a malformed conus medullaris was significantly associated with delayed independent walking (P = .014). The median age of independent walking in children with Morota's classification type 2 was 14 months, which is 1 month later compared to other types, although this difference was not significant (P = .055). Conclusion: Our findings suggest that complications arising from systemic combined anomalies and the presence of malformed conus medullaris are influencing factors in delays in independent walking in children with untethered lumbosacral lipomas.

Serotonin induces Arcadlin in hippocampal neurons.

The monoamine hypothesis does not fully explain the delayed onset of recovery after antidepressant treatment or the mechanisms of recovery after electroconvulsive therapy (ECT). The common mechanism that operates both in ECT and monoaminergic treatment presumably involves molecules induced in both of these conditions. A spine density modulator, Arcadlin (Acad), the rat orthologue of human Protocadherin-8 (PCDH8) and of Xenopus and zebrafish Paraxial protocadherin (PAPC), is induced by both electroconvulsive seizure (ECS) and antidepressants; however, its cellular mechanism remains elusive. Here we confirm induction of Arcadlin upon stimulation of an N-methyl-d-aspartate (NMDA) receptor in cultured hippocampal neurons. Stimulation of an NMDA receptor also induced acute (20 min) and delayed (2 h) phosphorylation of the p38 mitogen-activated protein (MAP) kinase; the delayed phosphorylation was not obvious in Acad-/- neurons, suggesting that it depends on Arcadlin induction. Exposure of highly mature cultured hippocampal neurons to 1-10 µM serotonin for 4 h resulted in Arcadlin induction and p38 MAP kinase phosphorylation. Co-application of the NMDA receptor antagonist d-(-)-2-amino-5-phosphonopentanoic acid (APV) completely blocked Arcadlin induction and p38 MAP kinase phosphorylation. Finally, administration of antidepressant fluoxetine in mice for 16 days induced Arcadlin expression in the hippocampus. Our data indicate that the Arcadlin-p38 MAP kinase pathway is a candidate neural network modulator that is activated in hippocampal neurons under the dual regulation of serotonin and glutamate and, hence, may play a role in antidepressant therapies.

Dendritic Spine Density is Increased in Arcadlin-deleted Mouse Hippocampus.

The neural network undergoes remodeling in response to neural activity and interventions, such as antidepressants. Cell adhesion molecules that link pre- and post-synaptic membranes are responsible not only for the establishment of the neural circuitry, but also for the modulation of the strength of each synaptic connection. Among the various classes of synaptic cell adhesion molecules, a non-clustered protocadherin, Arcadlin/Paraxial protocadherin/Protocadherin-8 (Acad), is unique in that it is induced quickly in response to neural activity. Although the primary structure of Arcadlin implies its cell adhesion activity, it weakens the adhesion of N-cadherin. Furthermore, Arcadlin reduces the dendritic spine density in cultured hippocampal neurons. In order to gain an insight into the function of Arcadlin in the brain, we examined the dendritic morphologies of the hippocampal neurons in Acad-/- mice. Acad-/- mice showed a higher spine density than wild-type mice. Following an electroconvulsive seizure (ECS), which strongly induces Arcadlin in the hippocampus, the spine density gradually decreased for 8 h. ECS did not reduce the spine density of CA1 apical dendrites in Acad-/- mice. Daily intraperitoneal injection of the antidepressant fluoxetine (25 mg/kg/day) for 18 days resulted in the induction of Arcadlin in the hippocampus. This treatment reduced spine density in the dentate gyrus and CA1. Chronic fluoxetine treatment did not suppress spine density in Acad-/- mice, suggesting that fluoxetine-induced decrease in spine density is largely due to Arcadlin. The present findings confirm the spine-repulsing activity of Arcadlin and its involvement in the remodeling of hippocampal neurons in response to antidepressants.