title: Posterior fossa decompression in Chiari I improves denervation of the paraspinal muscles.
abstract: To investigate whether posterior fossa decompression (PFD) could improve denervation of the paraspinal muscles in patients with Chiari I malformation (CMI).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Spine Surgery, Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Shifu
authors.initials: S
authors.lastname: Sha
authors.affiliation: Department of Spine Surgery, Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Spine Surgery, Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Spine Surgery, Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Spine Surgery, Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Spine Surgery, Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Spine Surgery, Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Spine Surgery, Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Spine Surgery, Drum Tower Hospital of Nanjing University Medical School, Nanjing, China zhuzezhang@nju.edu.cn.
authors.forename: Zezhang
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D001139:Arnold-Chiari Malformation / Q000601:surgery*; D003388:Cranial Fossa, Posterior / Q000601:surgery*; D019299:Decompression, Surgical; D003714:Denervation; D006801:Humans; D064170:Paraspinal Muscles; D012189:Retrospective Studies; D013595:Syringomyelia / Q000601:surgery
keywords: Chiari I malformation; apoptosis; denervation; paraspinal muscle; posterior fossa decompression