Delayed decompression exacerbates ischemia-reperfusion injury in cervical compressive myelopathy

Abstract

Degenerative cervical myelopathy (DCM) is the most common progressive nontraumatic spinal cord injury. The most common recommended treatment is surgical decompression, although the optimal timing of intervention is an area of ongoing debate. The primary objective of this study was to assess whether a delay in decompression could influence the extent of ischemia-reperfusion injury and alter the trajectory of outcome in DCM. Using a DCM mouse model, we show that decompression acutely led to a 1.5- to 2-fold increase in levels of inflammatory cytokines within the spinal cord. Delayed decompression was associated with exacerbated reperfusion injury, astrogliosis, and poorer neurological recovery. Additionally, delayed decompression was associated with prolonged elevation of inflammatory cytokines and an exacerbated peripheral monocytic inflammatory response (P < 0.01 and 0.001). In contrast, early decompression led to resolution of reperfusion-mediated inflammation, neurological improvement, and reduced hyperalgesia. Similar findings were observed in subjects from the CSM AOSpine North America and International studies, where delayed decompressive surgery resulted in poorer neurological improvement compared with patients with an earlier intervention. Our data demonstrate that delayed surgical decompression for DCM exacerbates reperfusion injury and is associated with ongoing enhanced levels of cytokine expression, microglia activation, and astrogliosis, and paralleled with poorer neurological recovery.

Late-onset “white cord syndrome” in an elderly patient after posterior cervical decompression and fusion: a case report

“…According to the above-mentioned hypothesis and based on experimental and epidemiologic studies the current literature suggests that the increased age of the patient, any comorbidities, and the chronic compression of the cord are potential risk factors and should be so identified. Specifically, recent experimental studies in mice models suggest that delayed decompression can exacerbate reperfusion injury and is associated with ongoing enhanced levels of cytokine expression, microglial activation, and astrogliosis [10], while early decompression inhibits the expression of TNF-α [24]. Furthermore, an extensive epidemiologic international study, noticed that older patients with comorbidities accompanied with severe and long-term compression of the cervical spinal cord undergoing surgical decompression, had a poorer functional outcome according to modified Japanese Orthopaedic Association score [9].…”

“…By this case report, we support the hypothesis that the reperfusion injury can also be subacute (until 24 h following decompression) [8], especially in an elderly population with atherosclerotic vessels, chronic hypertension, and other comorbidities [9], rather than being exclusively acute as in the three previous cases. Furthermore, delayed decompression exacerbates ischemia-reperfusion in cervical compressive myelopathy [10]. Spine surgeons should be aware of this extremely rare complication, not only intraoperatively but also postoperatively, in order to recognize this potential disastrous complication early on.…”

White Cord Syndrome: The Terrible Nightmare

“…This abnormality denotes prolonged compression of the cord leading to neuronal loss or myelomalacia and associated with poor outcome. Delayed decompression could exacerbate the reperfusion injury cascade as has been suggested in experimental study in mice [13]. In the previously reported 6 cases, four cases have hyperintense T2 signal area in the preoperative MRI.…”

&lsquo;White cord syndrome&rsquo;, a rare but disastrous complication of transient paralysis after posterior cervical decompression for severe cervical spondylotic myelopathy and spinal stenosis: A case report

“…Yang et al ( 1 ) reported that surgical decompression increased the expression of inflammatory cytokines, including TNF-α and IL-1β, in an animal model of chronic severe spinal cord compression. Similarly, Vidal et al ( 21 ) suggested that decompression led to a 1.5- to 2-fold increase in expression levels of inflammatory cytokines in a mouse model of DCM. It was also reported that delayed decompression aggravated ischemia-reperfusion injury, resulting in decreased neurological improvement compared with earlier intervention.…”

“…In another study, perioperative methylprednisolone treatment (30 min prior to decompression and 2 weeks after decompression at one dose of 30 mg/kg) reduced neurological deterioration caused by ischemia-reperfusion injury via its anti-inflammatory effect in a mouse model of DCM ( 22 ). In animal models, the levels of inflammatory cytokines such as TNF-α and IL-1β increased when decompression-associated spinal cord ischemia-reperfusion injury occurred, indicating that inflammatory cytokines may be considered as an important evaluation indicator of decompression-associated spinal cord ischemia-reperfusion injury ( 1 , 21 , 22 ).…”