A novel hypothesis about abnormalities in ependymal ciliary cytoskeleton driving the development of syringomyelia-associated scoliosis and its potential mechanism

Abstract

Syringomyelia is a chronic progressive disorder characterized by a fluid-filled syrinx inside the spinal cord that is frequently accompanied by scoliosis. As a prevalent type of neuromuscular scoliosis, the proper therapy for syringomyelia-associated scoliosis (SAS) is still under dispute. Many possible hypotheses have been proposed in the past, but the exact mechanism of how SAS occurs and progresses remains unknown. It is known that idiopathic scoliosis might have a neurological etiology involving bilateral asymmetric neural signal abnormalities in synaptic neurotransmission. Previous studies have shown that its etiology begins in the early stages of pathology, with abnormal cerebrospinal fluid (CSF) circulation in the subarachnoid space due to ependymal polarity deviation and ciliary beating disorder. Abnormal ependymal polarity and ciliary disorder are also core factors during the progression of syringomyelia. Therefore, this study proposes a novel hypothesis implicating abnormalities in the ependymal ciliary cytoskeleton as a driving factor in the development of SAS. Specifically, the underlying factors disturb the circulation of the CSF, which in turn leads to disorder of ependymal cellular polarity and the Actin network, with centrioles and cilia falling off under the shear stress of the CSF. On the one hand, CSF accumulates abnormally in the central canal, resulting in syringomyelia. On the other hand, abnormal ciliary motility fails to maintain normal assembly of Reissner fibers, which could affect the transmission of certain important neurotransmitters and destroy the left and right sides’ periodic alternating neuronal activity, eventually leading to the occurrence of spinal deformities related to syringomyelia. A novel perspective on the pathophysiology of SAS is presented with the possible mechanism of ependymal ciliary dynamics modulating the direction of the body axis under pathological conditions. These findings could also help orient future research and therapy.