Adolescent idiopathic scoliosis (AIS), cerebrospinal fluid (CSF) flow and ciliopathy

Abstract

AIS is a three-dimensional deformity of spine, affecting 1 to 3% of the population between 10 and 16 years. Its mechanism of occurrence is not known but polygenic initiating factors are admitted. Thus, Ptk7 mutant zebrafish have scoliosis associated with a change in CSF flow. The Ptk7 gene is an essential regulator of Wnt signaling pathway, involved in ciliary function. From this animal model, we hypothesize that some AIS are secondary to ciliopathy, with modification of CSF intramedullary flow. We present the results of a pilot feasibility study on the evaluation of CSF flow in AIS. Single-center study of 13 patients (12 girls and 1 boy, mean age 15.2 years) with AIS (mean Cobb's angle 33.7°; 6 left thoracolumbar curves, 5 right thoracic, 2 right lumbar). These patients required medullospinal MRI for various causes (rachialgia, suspicion of secondary scoliosis, preoperative assessment…). During this MRI (1.5 Tesla), an CSF flow analysis was performed (at the level of apical vertebra, and upper end vertebra and lower end vertebra). Of the 13 MRIs performed, 2 flow studies are not interpretable. The interpretable results show, at systole, a mean flow at thoracic level: 4.23 ± 0.47 cm/s. No difference was found between levels of scoliotic curvature (apical vertebra, upper and lower end vertebrae). Three patients had a pathological thoracic flow: 2 slowing down and 1 acceleration. In patient 1, the results showed a decrease of flow from 2.4 cm/s in T3 (level of T3 vertebra) to 0.8 cm/s in T7, in patient 2, a steady flow at 2.5 cm/s in thoracic and lumbar level, but physiologically there is a lumbothoracic gradient acceleration, and in patient 3 acceleration to 12.7 cm/sec in T6. This pilot study shows abnormalities of CSF flow in some patients with AIS. Our results require to be confirmed by a controlled study. Nevertheless, this result suggests that ciliary dysfunction may be an etiologic factor of AIS. Different etiologic pathways can be discussed involving the Wnt signaling pathway, the melatonin-signaling pathway or the cerebrospinal fluid-contacting neurons. Thanks to IMANORD-HPVA radiologic team.