Research ArticleSpinal Cord Injury

Riluzole blocks perioperative ischemia-reperfusion injury and enhances postdecompression outcomes in cervical spondylotic myelopathy

Science Translational Medicine  02 Dec 2015:
Vol. 7, Issue 316, pp. 316ra194
DOI: 10.1126/scitranslmed.aac6524

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Improving the odds for decompression surgery

Decompression surgery is generally effective in alleviating neurological impairment in patients with cervical spondylotic myelopathy (CSM), the most common cause of spinal cord dysfunction. In a new work, Karadimas et al. show that some patients with CSM experience neurological complications after decompression surgery. Using a rat model of CSM, the authors demonstrate that these complications are, in part, due to the rapid increase in blood flow after decompression of the compressed spinal cord. The FDA-approved drug riluzole can protect against injury after decompression surgery, reducing neurological complications and improving long-term outcomes beyond those seen with decompression surgery alone.

Abstract

Although surgical decompression is considered the gold standard treatment for cervical spondylotic myelopathy (CSM), a proportion of cases show postoperative decline or continue to exhibit substantial neurological dysfunction. To investigate this further, we first examined data from the prospective multicenter AOSpine North America CSM study, finding that 9.3% of patients exhibited postoperative functional decline (ΔmJOA, ≤−1) and that 44% of patients were left with substantial neurological impairment 6 months postoperatively. Notably, 4% of patients experienced perioperative neurological complications within 20 days after surgery in otherwise uneventful surgeries. To shed light on the mechanisms underlying this phenomenon and to test a combination therapeutic strategy for CSM, we performed surgical decompression in a rat model of CSM, randomizing some animals to also receive the U.S. Food and Drug Administration–approved drug riluzole. Spinal cord blood flow measurements increased after decompression surgery in rats. CSM rats showed a transient postoperative neurological decline akin to that seen in some CSM patients, suggesting that ischemia-reperfusion injury may occur after decompression surgery. Riluzole treatment attenuated oxidative DNA damage in the spinal cord and postoperative decline after decompression surgery. Mechanistic in vitro studies also demonstrated that riluzole preserved mitochondrial function and reduced oxidative damage in neurons. Rats receiving combined decompression surgery and riluzole treatment displayed long-term improvements in forelimb function associated with preservation of cervical motor neurons and corticospinal tracts compared to rats treated with decompression surgery alone.

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