92. Intrathecal pressure, spinal cord compression and edema following traumatic spinal cord injury in a porcine model

BACKGROUND CONTEXT Dural decompression is a potential treatment for SCI patients with persistent dural compression of the spinal cord. It may improve spinal cord tissue perfusion via reduced local intrathecal pressure (ITP). Clinically, injury-site ITP reductions have been observed with dural decompression of severely swollen spinal cords. In pigs, elevated pressure within the spinal cord parenchyma has been observed for 7 days following contusion SCI. PURPOSE The aim of this study was to characterize ITP at, and across, the injury site, for 14 days postinjury, in a domestic pig model, and to explore the relationship between ITP, intrathecal occlusion, and indicators of edema and inflammation. STUDY DESIGN/SETTING Institutional animal ethics committee approved study in a porcine model of spinal cord injury. OUTCOME MEASURES Motor function score, intrathecal pressure, intrathecal occlusion, quantitative histology. METHODS Animals received analgesia, anesthetics, and veterinary care across all procedures. Anesthetized female domestic pigs (26-34 kg), received a T10 contusion SCI with a custom device that released a 50 g impactor from 10 cm (n=3) or 20 cm (n=5) onto the exposed dura. A further two animals (P01/P02) received minimal SCI due to technical issues but their outcomes are retained for comparison. Three days prior to SCI, intrathecal catheters were surgically placed to allow insertion of miniature ITP sensors at T10 and ∼150 mm caudal/cranial. Animals were anesthetized at 3-, 7-, 10- and 14-days post-SCI for ITP measurements and magnetic resonance (MR) imaging. Hind limb motor function was assessed at 8- and 13-days post-SCI. Animals were transcardially perfused at 14 days post-SCI and spinal cord tissue was histologically analyzed to measure lesion volume, spared white matter, blood-spinal cord barrier permeability and microglia/macrophages. Statistics were not completed due to low animal numbers. RESULTS All SCI animals displayed hind limb motor deficits, with differences in stepping and weight bearing between the groups; bladder and bowel function was retained. Preinjury (T10: 4.8±1.0 mmHg) and ∼1hr postinjury mean ITP (T10: 4.4±0.8 mmHg) were consistent across animals and spinal levels. No systematic changes in mean ITP were observed across the time course or between injury groups, either at the injury site, or across the caudal and cranial locations; although, in some animals, injury-site ITP measurements were confounded by extradural compression of the thecal sac and cord. Post-SCI MR showed injury-site signal hyperintensity, and intrathecal occlusion resulting from cord swelling and hematoma overlying the T10 laminectomy site was common; occlusion typically reduced at day 7 and 14 post-SCI. Histological lesion volume was 20% greater, and 30% less white matter was spared, in the 20-cm group than in the 10-cm group. Barrier permeability and activated microglia/macrophage presence was elevated at the injury epicentre for both injury groups. CONCLUSIONS The apparent discordance between mean ITP changes, extradural compression, and histologic evidence of cord edema at 14 days postinjury, was unexpected. Injury site ITP measurements may have been confounded by the extradural compression around T10 and inconsistent effects of anesthesia on physiological variables that may influence ITP dynamics (e.g. BP, respiration) on measurement days. Acknowledgements. This study was funded, in part, by North American Spine Society [CFJ/AVL]; Conquer Paralysis Now [CFJ/AVL]; Depuy Synthes [CFJ/AVL]; The Hospital Research Foundation [CDG]; National Health and Medical Research Council (Australia) [CFJ]. FDA Device/Drug Status This abstract does not discuss or include any applicable devices or drugs. Dural decompression is a potential treatment for SCI patients with persistent dural compression of the spinal cord. It may improve spinal cord tissue perfusion via reduced local intrathecal pressure (ITP). Clinically, injury-site ITP reductions have been observed with dural decompression of severely swollen spinal cords. In pigs, elevated pressure within the spinal cord parenchyma has been observed for 7 days following contusion SCI. The aim of this study was to characterize ITP at, and across, the injury site, for 14 days postinjury, in a domestic pig model, and to explore the relationship between ITP, intrathecal occlusion, and indicators of edema and inflammation. Institutional animal ethics committee approved study in a porcine model of spinal cord injury. Motor function score, intrathecal pressure, intrathecal occlusion, quantitative histology. Animals received analgesia, anesthetics, and veterinary care across all procedures. Anesthetized female domestic pigs (26-34 kg), received a T10 contusion SCI with a custom device that released a 50 g impactor from 10 cm (n=3) or 20 cm (n=5) onto the exposed dura. A further two animals (P01/P02) received minimal SCI due to technical issues but their outcomes are retained for comparison. Three days prior to SCI, intrathecal catheters were surgically placed to allow insertion of miniature ITP sensors at T10 and ∼150 mm caudal/cranial. Animals were anesthetized at 3-, 7-, 10- and 14-days post-SCI for ITP measurements and magnetic resonance (MR) imaging. Hind limb motor function was assessed at 8- and 13-days post-SCI. Animals were transcardially perfused at 14 days post-SCI and spinal cord tissue was histologically analyzed to measure lesion volume, spared white matter, blood-spinal cord barrier permeability and microglia/macrophages. Statistics were not completed due to low animal numbers. All SCI animals displayed hind limb motor deficits, with differences in stepping and weight bearing between the groups; bladder and bowel function was retained. Preinjury (T10: 4.8±1.0 mmHg) and ∼1hr postinjury mean ITP (T10: 4.4±0.8 mmHg) were consistent across animals and spinal levels. No systematic changes in mean ITP were observed across the time course or between injury groups, either at the injury site, or across the caudal and cranial locations; although, in some animals, injury-site ITP measurements were confounded by extradural compression of the thecal sac and cord. Post-SCI MR showed injury-site signal hyperintensity, and intrathecal occlusion resulting from cord swelling and hematoma overlying the T10 laminectomy site was common; occlusion typically reduced at day 7 and 14 post-SCI. Histological lesion volume was 20% greater, and 30% less white matter was spared, in the 20-cm group than in the 10-cm group. Barrier permeability and activated microglia/macrophage presence was elevated at the injury epicentre for both injury groups. The apparent discordance between mean ITP changes, extradural compression, and histologic evidence of cord edema at 14 days postinjury, was unexpected. Injury site ITP measurements may have been confounded by the extradural compression around T10 and inconsistent effects of anesthesia on physiological variables that may influence ITP dynamics (e.g. BP, respiration) on measurement days. Acknowledgements. This study was funded, in part, by North American Spine Society [CFJ/AVL]; Conquer Paralysis Now [CFJ/AVL]; Depuy Synthes [CFJ/AVL]; The Hospital Research Foundation [CDG]; National Health and Medical Research Council (Australia) [CFJ].