Objective To investigate whether posterior fossa decompression (PFD) could improve denervation of the paraspinal muscles in patients with Chiari I malformation (CMI).
Background Paraspinal muscle denervation is one of the essential elements in the pathophysiology of CMI/syringomyelia-related scoliosis. Although PFD has been widely used for managing CMI, whether denervation of the paraspinal muscles may benefit from this neurosurgical procedure remains ambiguous. Bax and Bcl-2 are two regulators of apoptosis that are closely related to the innervation status of skeletal muscles, and denervation is associated with upregulated Bax and downregulated Bcl-2.
Methods Thirty-seven patients who underwent PFD and subsequent deformity correction for CMI-associated scoliosis were enrolled. Biopsy specimens were obtained from bilateral erector spinae muscles during both procedures with an average interval of 6.5 months. The biopsy site was located within the spinal innervation region involved by the syrinx and near the level of upper instrumented vertebra. The expression levels of Bax and Bcl-2 as well as histological features of the muscle fibres were examined at the two time points.
Results After PFD, the mRNA level of antiapoptotic Bcl-2 was elevated by 178% and 260% in the convex and concave muscles, respectively, with a coincident decrease of 69% and 73% for proapoptotic Bax at the corresponding sites (p<0.001). Consistent with the mRNA data, the Bcl-2 protein in the paraspinal muscles was increased by 75% on the convex and by 169% on the concave side following PFD. For Bax protein, decreases of 45% and 52% were detected in the convex and concave muscles, respectively (p<0.001). On average, these changes led to a 60% decrease in the Bax/Bcl-2 ratio, suggesting reduced apoptotic signalling and improved innervation of the paraspinal muscles. Histologically, the specimens demonstrated improvements in denervation-associated changes of the muscle fibres following PFD, with the number of atrophic and necrotic/degenerated fibres decreasing significantly from 6.7 and 8.5 before surgery to 3.2 (p=0.012) and 4.2 (p<0.001) after surgery, respectively.
Conclusion In patients with CMI, treatment with PFD led to a decrease in the Bax/Bcl-2 ratio at both the mRNA and protein levels, indicating an attenuated susceptibility to apoptotic cell death. These data, coupled with the observed improvements in histopathological features of the myofibres, suggest that PFD in Chiari I ameliorates denervation of the paraspinal muscles.
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Contributors SS, YQ, JJ and ZZ contributed to the study concept and design. YL, ZL, XS, ZF and WZ participated in data collection and processing. SS, YQ and ZF contributed to the analysis and interpretation of data. SS and YL wrote the manuscript. YQ, JJ and ZZ revised the manuscript for important intellectual content. ZZ provided study supervision and obtained funding.
Funding National Natural Science Foundation (Grant No. 81171672).
Competing interests None declared.
Patient consent Obtained.
Ethics approval Institutional Review Board of Nanjing Drum Tower Hospital.
Provenance and peer review Not commissioned; externally peer reviewed.
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