Background: Klippel-Feil syndrome (KFS) represents a rare anomaly characterized by congenital fusion of the cervical vertebrae. The underlying molecular etiology remains largely unknown because of the genetic and phenotypic heterogeneity.Methods: We consecutively recruited a Chinese cohort of 37 patients with KFS. The clinical manifestations and radiological assessments were analyzed and whole-exome sequencing (WES) was performed. Additionally, rare variants in KFS cases and controls were compared using genetic burden analysis.Results: We primarily examined rare variants in five reported genes (GDF6,MEOX1, GDF3, MYO18BandRIPPLY2) associated with KFS and detected three variants of uncertain significance inMYO18B. Based on rare variant burden analysis of 96 candidate genes related to vertebral segmentation defects, we identifiedBAZ1Bas having the highest probability of association with KFS, followed byFREM2,SUFU,VANGL1andKMT2D. In addition, seven patients were proposed to show potential oligogenic inheritance involving more than one variants in candidate genes, the frequency of which was significantly higher than that in the in-house controls.Conclusions: Our study presents an exome-sequenced cohort and identifies five novel genes potentially associated with KFS, extending the spectrum of known mutations contributing to this syndrome. Furthermore, the genetic burden analysis provides further evidence for potential oligogenic inheritance of KFS.

Background: Percutaneous kyphoplasty (PKP) has become an important minimally invasive surgical technique for fracture stabilization and pain relief in patients with vertebral compression fractures. However, intraspinal cement leakage following PKP is a serious postoperative complication that can lead to morbidity and mortality. Case presentation: We describe an uncommon case of epidural leakage of bone cement in an 81-year-old woman who underwent posterior lumbar decompression and fusion from L3–5 4 years prior and had an unremarkable postoperative course. The patient was admitted to Peking Union Medical College Hospital with complaints of muscle weakness and severe low back pain radiating to the left thigh 1 week after PKP of L5 due to an acute osteoporotic compression fracture. Computed tomographic imaging revealed massive leakage of cement into the spinal canal at L5-S1, and therefore, surgical decompression and removal of epidural cement were performed carefully without causing a dural tear. She improved remarkably and no neurologic deterioration was observed in the postoperative period during the one-year follow-up. Conclusions: We present the rare reported case, to our knowledge, of epidural cement leakage after PKP at the segment of internal fixation and discuss the most likely etiologies and preventive measures for this condition.

Neurological disorders affect a large population, often leading to different levels of disability and resulting in decreased quality of life. Due to the limited recovery obtained from surgical procedures and other medical approaches, a large number of patients with prolonged dysfunction receive neurorehabilitation protocols to improve their neural plasticity and regeneration. However, the poor neural regeneration ability cannot effectively rebuild the tissue integrity and neural functional networks; consequently, the prognoses of neurorehabilitation remain undetermined. To increase the chances of neural regeneration and functional recovery for patients with neurological disorders, regenerative rehabilitation was introduced with combined regenerative medicine and neurorehabilitation protocols to repair neural tissue damage and create an optimized biophysical microenvironment for neural regeneration potential. With the deepening of exosome research, an increasing number of studies have found that the systemic therapeutic effects of neurorehabilitation approaches are mediated by exosomes released by physically stimulated cells, which provides new insight into rehabilitative mechanisms. Meanwhile, exosome therapy also serves as an alternative cell-free therapy of regenerative medicine that is applied in partnership with neurorehabilitation approaches and formulates exosome-based neurological regenerative rehabilitation. In this study, we review the current state of exosome-associated neurorehabilitation. On the one hand, we focus on presenting the varied mediating effects of exosomes in neurorehabilitation protocols of specific neurological pathologies; on the other hand, we discuss the diverse combinations of exosome therapies and neurorehabilitation approaches in the field of neurological regenerative rehabilitation, aiming to increase the awareness of exosome research and applications in the rehabilitation of neurological disorders.

Background: Klippel-Feil syndrome (KFS) represents the rare and complex deformity characterized by congenital defects in the formation or segmentation of the cervical vertebrae. There is a wide gap in understanding the detailed mechanisms of KFS because of its rarity, heterogeneity, small pedigrees, and the broad spectrum of anomalies. Methods: We recruited eight patients of Chinese Han ethnicity with KFS, five patients with congenital scoliosis (CS) who presented with congenital fusion of the thoracic or lumbar spine and without known syndrome or cervical deformity, and seven healthy controls. Proteomic analysis by data-independent acquisition (DIA) was performed to identify the differential proteome among the three matched groups and the data were analyzed by bioinformatics tools including Gene Ontology (GO) categories and Ingenuity Pathway Analysis (IPA) database, to explore differentially abundant proteins (DAPs) and canonical pathways involved in the pathogenesis of KFS. Results: A total of 49 DAPs were detected between KFS patients and the controls, and moreover, 192 DAPs were identified between patients with KFS and patients with CS. Fifteen DAPs that were common in both comparisons were considered as candidate biomarkers for KFS, including membrane primary amine oxidase, noelin, galectin-3-binding protein, cadherin-5, glyceraldehyde-3-phosphate dehydrogenase, peroxiredoxin-1, CD109 antigen, and eight immunoglobulins. Furthermore, the same significant canonical pathways of LXR/RXR activation and FXR/RXR activation were observed in both comparisons. Seven of DAPs were apolipoproteins related to these pathways that are involved in lipid metabolism. Conclusions: This study provides the first proteomic profile for understanding the pathogenesis and identifying predictive biomarkers of KFS. We detected 15 DAPs that were common in both comparisons as candidate predictive biomarkers of KFS. The lipid metabolism-related canonical pathways of LXR/RXR and FXR/RXR activation together with seven differentially abundant apolipoproteins may play significant roles in the etiology of KFS and provide possible pathogenesis correlation between KFS and CS.