ABSTRACT
The mammalian spinal cord functions as a community of cell types for sensory processing, autonomic control, and movement. While animal models have advanced our understanding of spinal cellular diversity, characterizing human biology directly is important to uncover specialized features of basic function and human pathology. Here, we present a cellular taxonomy of the adult human spinal cord using single-nucleus RNA sequencing with spatial transcriptomics and antibody validation. We identified 29 glial clusters and 35 neuronal clusters, organized principally by anatomical location. To demonstrate the relevance of this resource to human disease, we analyzed spinal motoneurons, which degenerate in amyotrophic lateral sclerosis (ALS) and other diseases. We found that compared with other spinal neurons, human motoneurons are defined by genes related to cell size, cytoskeletal structure, and ALS, suggesting a specialized molecular repertoire underlying their selective vulnerability. We include a web resource to facilitate further investigations into human spinal cord biology.
Subject(s)
Amyotrophic Lateral Sclerosis , Animals , Humans , Adult , Amyotrophic Lateral Sclerosis/metabolism , Spinal Cord/metabolism , Motor Neurons/metabolism , Models, Animal , Neuroglia/metabolism , MammalsABSTRACT
BACKGROUND: Painful vertebral compression fractures (VCFs) in myeloma patients severely reduce quality of life. Currently, the International Myeloma Working Group (IMWG) and National Institute of Clinical Excellence NICE advocate the use of either balloon kyphoplasty or vertebroplasty in the management of these fractures. METHODS: All patients with VCFs and myeloma who adhered to the IMWG indications for vertebral augmentation were treated with the Osseofix® implant. Visual analogue scores (VAS) and Oswestry disability index (ODI) were taken preoperatively and at least one year following surgery. Cobb angle and implant migration were measured on lateral standing radiographs. RESULTS: Sixteen patients (average age 62, SD = 11.6) consisting of 82 levels (range 3-8) were stabilised with no perioperative complications or revisions at one year. There was an improvement in patient-reported outcomes with the median preoperative VAS of 8.6 (IQR 7.3-10.0) reducing to 3 (IQR 1.0-4.0) after one year (P < 0.001) whilst an average improvement of 31.4 (SD = 19.6) points in the ODI scores was reported (P < 0.001). There was no significant collapse or implant failure at one year with a greater improvement in the VAS/ODI score, when more implants were used (P = 0.049 and 0.008, respectively). The average length of stay was 2.2 days (SD = 1.7). CONCLUSION: The use of the Osseofix® implant in VCFs caused by multiple myeloma has shown a statistically significant improvement in both pain and outcome scores. There were no complications or significant radiological deterioration of spinal alignment over the course of a year.