The Role of Magnesium in the Secondary Phase After Traumatic Spinal Cord Injury. A Prospective Clinical Observer Study.

André Sperl,Bahram Biglari,Patrick Haubruck,Raban Arved Heller,Julian Seelig,Arash Moghaddam,Lutz Schomburg,Tobias Bock

doi:10.3390/antiox8110509

Abstract

In the secondary injury phase after traumatic spinal cord injury (TSCI), oxidative stress and neuroinflammatory responses at the site of injury constitute crucial factors controlling damage extent and may serve as potential therapeutic targets. We determined Magnesium (Mg) serum concentration dynamics in context with the potential of neurological remission in patients with TSCI as Mg is suspected to limit the production of reactive oxygen species and reduce lipid peroxidation. A total of 29 patients with acute TSCI were enrolled, and blood samples were drawn over 3 months at 11 time-points and Mg quantification was performed. Patients were divided into those with (G1, n = 18) or without neurological remission (G0, n = 11). Results show a slight drop in Mg level during the first 4 h after injury, then remained almost unchanged in G1, but increased continuously during the first 7 days after injury in G0. At day 7 Mg concentrations in G1 and G0 were significantly different (p = 0.039, G0 > G1). Significant differences were detected between patients in G1 that presented an AIS (ASIA Impairment Scale) conversion of 1 level versus those with more than 1 level (p = 0.014, G1 AIS imp. = +1 > G1 AI imp. > +1). Low and decreasing levels of Mg within the first 7 days are indicative of a high probability of neurological remission, whereas increasing levels are associated with poor neurological outcome.

Highlights

At present, there is no effective neuroprotective or neuroregenerative therapy for patients with traumatic spinal cord injury (TSCI), despite the potential devastating consequences with life-long disabilities and a permanent need of multidisciplinary treatment including surgery, medication, Antioxidants 2019, 8, 509; doi:10.3390/antiox8110509 www.mdpi.com/journal/antioxidantsAntioxidants 2019, 8, 509 and long-term rehabilitation
The final degree of impairment can only be determined after the fourth phase; whereas, clinical experience shows if no improvement of complete impairment (AIS (ASIA Impairment Scale) grade A) can be observed within 72 h after injury, chances are inferior to reach any remission [7,8], making the immediate and early acute phase of the secondary injury phase after TSCI especially interesting as neuroprotective agents might be able to improve the outcome when administered during this period
We investigated the serum concentrations of Mg in adults subsequent to TSCI and tested for a possible correlation between dynamic changes in Mg levels and clinical outcomes

Summary

Introduction

There is no effective neuroprotective or neuroregenerative therapy for patients with traumatic spinal cord injury (TSCI), despite the potential devastating consequences with life-long disabilities and a permanent need of multidisciplinary treatment including surgery, medication, Antioxidants 2019, 8, 509; doi:10.3390/antiox8110509 www.mdpi.com/journal/antioxidantsAntioxidants 2019, 8, 509 and long-term rehabilitation. (IV) increased spasticity and hyperreflexia of cutaneous and deep tendon reflexes characterize the final phase and can last between 1–12 months. The final degree of impairment can only be determined after the fourth phase; whereas, clinical experience shows if no improvement of complete impairment (AIS (ASIA Impairment Scale) grade A) can be observed within 72 h after injury, chances are inferior to reach any remission [7,8], making the immediate and early acute phase of the secondary injury phase after TSCI especially interesting as neuroprotective agents might be able to improve the outcome when administered during this period. Recent and compelling evidence demonstrated significant fluxes of Mg2+ across the plasma membrane [10,11,12,13], affecting cell function and metabolic cycles triggered by various stimuli, such as hormones or secondary messenger-proteins. Mg accumulation is mediated by Mg-channels such as TRPM6 [14] and TRPM7 [15], while outward Mg transfer is mainly operated by Mg exchangers [16,17]

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