The changes in systemic monocytes in humans undergoing surgical decompression for degenerative cervical myelopathy may influence clinical neurological recovery

J Neuroimmunol. 2019 Nov 15:336:577024. doi: 10.1016/j.jneuroim.2019.577024. Epub 2019 Aug 16.

Abstract

Background: Degenerative cervical myelopathy (DCM) is the most common cause of non-traumatic spinal cord injury worldwide. Surgical decompression is recommended as the preferred treatment strategy for DCM as it halts disease progression and improves neurologic symptoms. We previously demonstrated that neuroinflammation, including monocytes, plays a critical role in the pathobiology of DCM and in ischemic-reperfusion injury (IRI) following surgical decompression. Monocytes are able to enter the spinal cord and brain tissues due to damage to the blood spinal cord and blood brain barrier following injury. Studies have demonstrated that stroke patients and individuals undergoing hip replacement surgery have increased systemic levels of monocytes. Additionally, changes in the signalling responses of monocytes are associated with post-surgical recovery or with ischemic neural tissue damage. Herein, we investigated the role of systemic monocytes as a predictive biomarker for clinical recovery following decompressive surgery for DCM.

Findings: There was a 2-fold increase in the number of monocytes in DCM patients at 24 h following decompression as compared to baseline levels, which was associated with a significant improvement in the modified Japanese Orthopedic Association scale (mJOA) at 6-months after surgery (p < .0001). In a mouse model of DCM, depleting acute monocytes reduced the non-classical (Ly6Clow) subset from circulation (p < .05) and resulted in a 1.8-fold increase in CD11b expression in the spinal cord at 5 weeks following decompression. Acute monocyte depletion was accompanied by a modest decline in long-term overground locomotion, as evidenced by significantly reduced hindlimb swing speed.

Conclusions: This work demonstrated that decompressive surgery leads to an acute increase in peripheral monocytes in human DCM patients, which is modestly associated with clinical recovery. We anticipate that this work could contribute to the implementation of routine measurements of blood monocyte subsets, their activation state, and production of cytokines following decompressive surgery. This information could help to select perioperative anti-inflammatory treatments that can enhance the beneficial effects of decompressive surgery and reduce the incidence of post-operative complications, while avoiding a reduction in systemic monocytes.

Keywords: Decompression; Degenerative cervical myelopathy (DCM); Monocytes; Non-classical monocytes; Systemic inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Cervical Vertebrae / surgery*
  • Decompression, Surgical / adverse effects
  • Decompression, Surgical / trends*
  • Female
  • Humans
  • Locomotion / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Monocytes / metabolism*
  • Postoperative Complications / blood
  • Postoperative Complications / etiology
  • Prospective Studies
  • Random Allocation
  • Recovery of Function / physiology*
  • Retrospective Studies
  • Spinal Cord Diseases / blood*
  • Spinal Cord Diseases / surgery*