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

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.

• Authors: Spyridon K Karadimas, Alex M Laliberte, Lindsay Tetreault, Young Sun Chung, Paul Arnold, Warren D Foltz, Michael G Fehlings
• Journal: Science translational medicine (Sci Transl Med) Vol. 7 Issue 316 Pg. 316ra194 (Dec 02 2015) ISSN: 1946-6242 [Electronic] United States
• PMID: 26631633 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Association for the Advancement of Science.

Chemical References

• Neuroprotective Agents
• Riluzole

Topics

• Animals
• Axons (pathology)
• Cervical Vertebrae (pathology)
• Decompression, Surgical
• Disease Models, Animal
• Humans
• Magnetic Resonance Imaging
• Motor Neurons (pathology)
• Neuroprotective Agents (therapeutic use)
• Prospective Studies
• Rats
• Reperfusion Injury (drug therapy)
• Riluzole (therapeutic use)
• Spinal Cord (pathology)
• Spinal Cord Diseases (drug therapy, surgery)
• Spondylosis (drug therapy, surgery)
• Treatment Outcome