Developing a Lifetime Cost Calculator for Spinal Cord Injury: The SCI Cost Calculator.

AANS: American Association of Neurological Surgeons AIS: Abbreviated Injury Scale ASIA: American Spinal Injury Association CNS: Congress of Neurological Surgeons CSFD: cerebrospinal fluid drainage FDA: Food and Drug Administration FGF: fibroblast growth factor G-CSF: granulocyte colony-stimulating factor HGF: hepatocyte growth factor IL: interleukin iPSC: induced pluripotent stem cell MAP: mean arterial blood pressure MPSS: methylprednisolone sodium succinate MSC: mesenchymal stem cell NASCIS: National Acute Spinal Cord Injury Studies Nogo: neurite outgrowth inhibitor NgR: Nogo receptor NPC: neural precursor cell NSS: Neuro-Spinal Scaffold OEC: olfactory ensheathing cell OPC: oligodendrocyte progenitor cell PEG: polyethylene glycol PLGA: poly(lactic-co-glycolic acid) SCI: spinal cord injury TH: therapeutic hypothermia TNF: tumor necrosis factor Traumatic spinal cord injury (SCI) is a devastating event caused by trauma to the spine which leads to mechanical disruption of the spinal cord. The incidence of SCI varies worldwide. Focusing on developed regions, North America (39 per million) has a higher annual incidence than Australia (16 per million) or Western Europe (15 per million).1 Direct costs for lifetime patient care reach $1.1 to 4.6 million per patient, which further underscores the need for the development of effective SCI treatments.2 Substantial research effort has been dedicated to uncovering the pathophysiology of SCI. This has led to the development of pharmacologic and cell-based therapies, which are now demonstrating functional motor recovery in animal models. Among these, several promising therapeutic agents are already being investigated in clinical trials for SCI. This review will summarize the pathophysiology and current evidence-based clinical strategies to manage an acute spinal cord injury followed by a discussion of key emerging treatments including pharmacological approaches, cell-based therapies, biomaterials and physiological approaches. PATHOPHYSIOLOGY Phases of SCI Tissue damage after SCI has been divided into primary and secondary injury phases.3,4 The physical forces of the initial trauma cause the primary injury and this is the main determinant of the severity of SCI. The axons, blood vessels, and cell membranes are disrupted by physical forces such as compression, shearing, laceration, and acute stretch. Secondary injury refers to delayed, progressive damage which continues after the primary injury and represents an additional important determinant of neurological deficits (Figure).5,6 Due to the disruption of the blood–spinal cord barrier following the primary injury, infiltration of inflammatory cells such as macrophages, microglia, T-cells, and neutrophils can be observed. Inflammatory cytokines such as tumor necrosis factor (TNF) α, interleukin (IL)-1α, IL-1β, and IL-6 are released by these cells, with levels of these cytokines peaking 6 to 12 h after injury and remaining elevated up to 4 d after injury.7 Increases in intracellular calcium are caused by the disruption of ionic homeostasis after SCI and activates calcium-dependent proteases (eg, phospholipases, calpain, caspase, and nitric oxide synthase). These proteases trigger dysfunction of mitochondria which leads to cell death.8 Oligodendrocytes are highly susceptible to apoptotic loss and apoptosis has been observed, not only at the lesion epicenter, but also distant from the epicenter leading to demyelination of preserved axons.9-11 Furthermore, delayed necrosis and apoptosis are induced by reactive oxygen species which are released by phagocytic inflammatory cells.12-14 Moreover, the disrupted cells release excitatory amino acids (eg, glutamate and asparate) after SCI15,16 and the excessive activation of excitatory amino acid receptors causes further loss of neurons and glia by both necrotic and apoptotic cell death.17 To achieve repair and regeneration of the injured spinal cord, researchers have attempted to disrupt elements of the secondary injury pathway with the aim of neural preservation, inhibition of the barriers to axonal regeneration, and replacement of the damaged cells by cell transplantation therapy. From a pathophysiological perspective, it is likely that the optimal therapy will be a combinatorial one consisting of administration of drugs to reduce secondary injury at the acute phase, followed by cell transplantation or other regenerative therapies to regenerate the damaged spinal cord tissue in the subacute to chronic phases.18,19 These therapies are discussed in greater detail below.FIGURE: Three pathophysiological phases after SCI including acute (eg, hemorrhage, edema, and inflammation), subacute (eg, demyelination and axonal dieback), and chronic (eg, cavity formation) phases. Primary injury is caused by the physical forces of the initial traumatic event. Secondary injury refers to delayed, progressive damage which includes inflammation, loss of ionic homeostasis, oxidative damage, excitotoxicity, apoptosis, and necrosis. Oligodendrocytes are highly susceptible to apoptotic loss resulting in axonal demyelination. Cystic cavitation forms in the center of the spinal cord, with surrounding glial scar in the subacute and chronic phases. Nonastrocyte cells mainly form a chemical barrier by secreting growth inhibitory CSPGs.Barriers to Regeneration The adult mammalian Congress of Neurological Surgeons (CNS), including the spinal cord, has generally been considered to have limited regenerative capacity due to the finite number of available regenerative cells and the restricted plasticity of the adult CNS.20 While recent research has shown that the spinal cord has more regenerative capacity than was previously thought,21,22 compared with the peripheral nervous system, the regenerative capacity of the CNS is lower and it gradually decreases with increasing age.23 Schwab et al24 reported the inhibitory nature of CNS myelin in 1985. Myelin-associated proteins, such as neurite outgrowth inhibitor A (Nogo A),25,26 oligodendrocyte-myelin glycoprotein,27 and myelin-associated glycoprotein28,29 function through Nogo receptors (NgR). The NgRs lack an intracellular signaling domain and transduce inhibitory signals by forming coreceptor complexes with TNF receptor family proteins (eg, p75, TROY, and LIGO-1) to activate the GTPase Rho A. The downstream effector of Rho A is Rho-associated protein kinase which affects changes in the actin cytoskeleton and leads to growth cone collapse of regenerating axons, neurite retraction, and increasing apoptosis. SCI is accompanied by mechanically induced and excitotoxic cell death, with associated demyelination. The lost parenchyma is replaced by cystic cavitation and regeneration is often hindered by the presence of this cystic cavity which lacks the substrate to support axonal growth and cell migration.30 Furthermore, at the site of injury, glial and fibrotic scarring is also present (Figure). Glial and fibrotic scarring results when pericytes, hypertrophied astrocytes, fibroblast lineage cells, and inflammatory cells form a physical barrier, walling off injured tissue from healthy tissue.31,32 Recent research has shown that both astrocytes and nonastrocyte cells can form a physical and chemical barrier by secreting growth inhibitory chondroitin sulfate proteoglycans (CSPGs) such as neurocan, versican, brevican, phosphacan, and NG2.33 A fibroblast-derived scar can also be located in the perilesional region and is associated with the deposition of inhibitory extracellular matrix molecules. Similar to myelin-associated inhibitors, these molecules act as chemical barriers to the regeneration of axons. CURRENT CLINICAL STRATEGIES Early Surgical Intervention To reduce the effects of cord compression and resultant ischemia, early bony and ligamentous surgical decompression is performed to provide relief from the mechanical pressure. To elucidate the effectiveness of early decompression, a prospective cohort study, The Surgical Treatment of Acute Spinal Cord Injury Study (STASCIS) was conducted with 313 cervical SCI patients.34 After adjusting for confounders, the early decompression group (<24 h after SCI) was 2.8 times as likely to demonstrate an Abbreviated Injury Scale (AIS) improvement of 2 or more grades at 6 mo after SCI compared with the late decompression group (≥24 h after SCI). A subsequent prospective Canadian cohort study (including cervical, thoracic, and lumbar SCI, n = 84) also revealed that early decompression was associated with a 2 or more grade AIS improvement at the time of rehabilitation facility discharge.35 The findings of these studies support the concept of "Time is Spine" which emphasizes the importance of early diagnosis and intervention to improve long-term outcomes. Central Cord Syndrome Central cord injury is characterized by greater weakness in the upper extremities than the lower extremities, variable sensory loss, variable bowel/bladder dysfunction, and, usually, early rapid improvements in neurological function. Early decompression has traditionally been avoided in cases of central cord injury with patients being allowed to plateau in their recovery over a number of weeks before any intervention.36 However, for patients with pre-existing canal stenosis, recent evidence suggests that early surgery may improve long-term outcomes. A systematic review demonstrated that patients undergoing early decompression (<24 h after SCI) had American Spinal Injury Association (ASIA) motor scores that were 6.31 points higher, and a greater chance of improvement in ASIA grade (odds ratio of 2.81) at 12-mo follow-up than those undergoing late decompression (≥24 h after SCI).37 Although the prospective randomized controlled Comparing Surgical Decompression Versus Conservative Treatment in Incomplete Spinal Cord Injury (COSMIC, NCT01367405) trial was initiated in 2013, it was terminated in 2016 due to difficulties in enrolling patients. Blood Pressure Augmentation The neuroprotective effects of blood pressure augmentation act through enhancing systemic perfusion. Several studies have shown that high-normal mean arterial blood pressures (MAPs) of 85 to 90 mm Hg may improve outcomes in SCI patients.38-40 The guidelines of the American Association of Neurological Surgeons (AANS) and (CNS) recommend MAP targets of 85 to 90 mm Hg as an option in SCI to be initiated as early as possible and maintained for 7 d after injury.41 This MAP elevation requires invasive blood pressure monitoring, maintenance of slightly hypervolemic state, and central venous access for continuous infusion of vasopressors. A noninferiority trial named Mean Arterial Blood Pressure Treatment for Acute Spinal Cord Injury (MAPS; NCT02232165) comparing MAP ≥ 85 mm Hg and MAP ≥ 65 mm Hg has been developed to assess the efficacy of lower targets. ASIA motor scores at 1 yr postinjury will be evaluated, and this trial is expected to complete in March 2017. Steroids for SCI Methylprednisolone sodium succinate (MPSS) is the only agent from completed clinical trials that has entered clinical use. It acts by reducing oxidative stress to enhance neural cell survival in animal models of traumatic SCI. Three landmark National Acute Spinal Cord Injury Studies (NASCIS) examined the use of MPSS for acute SCI.42-47 Although no neurological benefit in the MPSS-treated group was observed in the overall analyses of these studies, a subgroup analysis in the NASCIS II and III trials demonstrated that use of the drug in a higher dosing regimen than that used in NASCIS I within 8 h of injury resulted in neurological improvement, and that MPSS bolus 3 to 8 h after injury improved neurological function when it was administered for 48 h rather than 24 h.44-47 Recent evidence further supports the use of MPSS for SCI. A 2012 Cochrane meta-analysis and review demonstrated a 4 point greater ASIA motor score improvement in the group that received MPSS for acute SCI and that its administration was not associated with a significant increase in the risk of complications.48 Nevertheless, the 2013 AANS/CNS Section on Disorders of the Spine and Peripheral Nerves guideline provided a level I recommendation against the administration of MPSS which represents a marked change from the previous version despite little change in the evidence considered. Accordingly, an updated AOSpine guideline suggests that 24 h of MPSS IV be administered within 8 h of SCI to patients without medical contraindication.49 Emerging Therapies for SCI Key emerging technologies for SCI treatment include pharmacological approaches, cell-based therapies, biomaterials, and physiological approaches. A summary of these technologies is provided in Table.TABLE: Key Emerging Technologies for Acute SCIPharmacological Approaches Riluzole Riluzole is a benzothiazole antiepileptic which acts via sodium channel blockade. It is approved by the US Food and Drug Administration (FDA), European Medicines Agency, and Health Canada for the treatment of amyotrophic lateral sclerosis.50,51 Its role in neuroprotection stems from its ability to mitigate excitotoxicity and block sodium influx to neurons in addition to restricting the presynaptic release of glutamate.52 In animal studies, Riluzole has been shown to reduce neuronal loss and cavity size which led to improvements in motor function and electrophysiology.53-55 In the phase I trial for acute SCI was recently completed, and 36 patients were enrolled.56 Although elevations of liver enzyme levels were observed temporarily, no serious adverse events were attributed to the drug. Regarding the neurological outcomes, cervical SCI patients treated with riluzole showed the better improvement in ASIA motor score compared with non-riluzole treated patients matched from an historical registry cohort. The phase II/III RCT entitled riluzole in Spinal Cord Injury Study (RISCIS; NCT01597518) is recruiting patients with acute C4-8 injuries with ASIA grade A, B, or C and will compare riluzole versus placebo and assess AIS, Spinal Cord Independence Measure, and brief pain inventory. This study which was initiated in 2014 has to date recruited 70 patients and is expected to conclude in 2020. Minocycline Minocycline is a second-generation semisynthetic tetracycline antibiotic that has the ability to cross the blood–brain barrier. It also has potent anti-inflammatory properties and inhibits microglial activation, TNF-α, IL-1β, cyclooxygenase-2, and matrix metalloproteinases.57-60 In animal studies, minocycline treatment after acute SCI has been shown to protect against neuron loss and reduce the lesion size.61,62 A phase II study showed that patients with incomplete cervical SCI (n = 25) demonstrated an ASIA score improvement of 14 points with minocycline treatment compared to placebo (P = .05).63 The follow-up Phase III Minocycline in Acute Spinal Cord Injury (MASC; NCT01828203) study will compare IV minocycline for 7 d and is expected to conclude in 2018. VX-210 (Cethrin) The Rho pathway is known to negatively impact axonal and neurite growth.64 A toxin produced by Clostridium botulinum, C3 transferase (cethrin), has been shown to inhibit Rho-mediated inhibition of axonal growth which promoted neural regeneration and motor function recovery in rodent SCI models.65 Cethrin is a permeable material intended for application to the dura mater at the site of SCI during decompressive surgery in the acute phase. A phase I/IIa multicenter, dose-escalation human trial evaluating this drug in a human population was published in 201166; no serious adverse events were attributed to the drug.66 Cervical patients treated with 3 mg of cethrin showed improvement in ASIA motor score at 12 mo and this was shown to be superior to historical recovery rates. A phase IIb/III study of cethrin has commenced in cervical SCI patients in 2016 and is expected to conclude in 2018. Anti-Nogo-A antibody (ATI-355) A monoclonal antibody of major inhibitory fractions within CNS myelin, IN-1, has been shown to promote axonal sprouting and functional recovery following SCI in animal models.67 The humanized anti-Nogo antibody, ATI-355, has been shown to promote axonal sprouting and functional recovery following SCI in numerous animal models and is a rare therapeutic in that it has been demonstrated to improve functional outcomes in a primate model.26 A phase I human trial of humanized anti-Nogo antibody (ATI-355) was completed in Europe, rather than the US, as the FDA expressed concerns with the infusion pump. Although this trial has been completed, it has not been published. A phase II study of ATI-355 is about to commence in Europe. Granulocyte Colony Stimulating Factor Granulocyte colony-stimulating factor (G-CSF) has been shown to increase the mobilization of bone marrow stromal cells from the bone marrow and to increase their presence at the site of SCI. In a rodent model, G-CSF enhances neurogenesis, reduces apoptosis, and decreases expression of TNF-α and IL-1β. These positive effects are associated with white matter sparing and improved hind-limb function.68 The phase I/IIa trials, which were nonrandomized, showed no increase in serious adverse events with G-CSF administration alongside AIS grade improvement.69,70 G-CSF is currently in a phases III clinical trial in Japan with results expected in 2018. Hepatocyte Growth Factor Hepatocyte growth factor (HGF) is mainly secreted by mesenchymal cells and promotes cellular growth and motility. HGF enhances neuron survival, decreases lesion size, and reduces oligodendrocyte apoptosis to improve behavioral outcomes in rodent models.71 Moreover, in a primate model of cervical SCI, HGF improved hand dexterity which is one of the most important key functions of the upper limb.72 A phase I/II clinical trial (NCT02193334) comparing intrathecal HGF (KP100IT) versus placebo is now underway with results expected in 2017. Magnesium (AC105) Magnesium is a physiological antagonist of NMDA receptors which decreases excitotoxicity and also functions as an anti-inflammatory agent. Magnesium with polyethylene glycol (PEG) improves cerebrospinal fluid levels without requiring large magnesium doses.73-75 The use of magnesium with PEG in the treatment of animal models of SCI has been shown to enhance tissue sparing and improve motor functional recovery.76,77 However, a phase I/II clinical trial (NCT01750684) of magnesium with PEG (AC105) was terminated in 2015 due to difficulties in enrolling patients. Fibroblast Growth Factor Fibroblast growth factor (FGF) plays a key role in preserving motor neurons adjacent to the SCI site and reduces acute respiratory deficits resulting from the loss of ventral horn neurons by reducing glutamate-mediated excitotoxicity in animal models.78,79 Although a phase I/II trial (NCT01502631) of the FGF-analog (SUN13837) has been completed, the results have not been published to date. Cell-Based Therapies Regenerative therapies based on transplanted multipotent and differentiated cells are an exciting therapeutic approach showing promising results in translational studies. Initial research focused on embryonic stem cell lines derived from aborted early-stage embryos, however, ethical considerations and limited numbers of donor cells created challenges. More recently, the discovery of induced pluripotent stem cells (iPSCs), which can be derived within weeks from any somatic cell source, has revolutionized the field by providing a nearly limitless source of pluripotent cells for research and therapeutic purposes.80 Furthermore, iPSCs can potentially be derived from autologous tissue reducing or eliminating the risk of graft rejection.80 While unforeseen challenges in iPSC technology, such as epigenetic memory and early senescence, have been found, they continue to be a substantial technological advance in spinal cord regeneration.81 The most translationally relevant cell therapies derived from pluripotent stem cells or harvested from adult tissue are discussed cells are known to peripheral regeneration by providing a and support to axons. In rodent models of SCI, have been shown to reduce lesion size, axons, and provide motor The to has a phase trial (n = to assess for patients with chronic AIS grade injuries in the cervical or The study is expected to conclude in 2018. additional phase I trial (n = of derived for AIS grade A injuries has with results expected in ensheathing cells olfactory neurons and provide from and the In animal models of SCI, they have been to enhance neurite outgrowth and resulting in significant functional the are now and for chronic While a meta-analysis of several of these trials (n = no increase in serious adverse efficacy has to be due to concerns within the A previous study showed the of transplanted on from the into the spinal clinical trials of for chronic SCI have been completed and in a meta-analysis which no significant increase in to the stem cells are multipotent tissue cells of into and to repair ability to the and systemic inflammatory led to their application in SCI they were to promote tissue sparing through signaling and of is now a Phase II/III randomized trial of autologous via and intrathecal for patients with AIS grade cervical SCI within 12 mo of The study is expected to conclude in precursor cells are multipotent CNS cells of to astrocytes, and to lost cells and provide are most the central canal of the spinal cord and after however, their numbers are limited of or stem a promising In animal models of cervical and SCI, transplanted have been shown to reduce cystic axons, and improve behavioral outcomes over In 2 phase II trials led by were terminated early due to The studies were the effects of human CNS stem cell for and cervical The results of these trials have not been however, provide evidence that cell are in on emerging it is likely that further to the transplanted cells their will be to enhance motor outcomes. progenitor cells have multipotent to but they to to axons. Several studies have and functional recovery after A phase I/II trial (n = is now underway by to assess with results expected by have the of several of biomaterials with to SCI. These can be with stem cells, to growth and can be to over Moreover, they are being to cavitation with a that the extracellular In rodent biomaterials such as and have been shown to improve and behavioral to clinical Neuro-Spinal Scaffold is a and poly(lactic-co-glycolic currently in phase III trial by n = The trial will the effects of in with AIS grade A injuries and no as a was provided by the FDA this a The study is expected to conclude by Approaches to to via a of has been shown to reduce CNS injury after and These reduce the of the CNS and the systemic inflammatory to SCI, is tissue sparing and improvements in behavioral recovery in the In patients with AIS grade A a study (n = early therapeutic hypothermia to be associated with better neurological A phase II/III trial by the to entitled for Traumatic of the currently The study will assess of initiated within 6 h of injury to both efficacy and treatment is known to be a of the secondary injury Similar to MAP cerebrospinal fluid drainage to improve early spinal cord pressure to reduce the While an initial trial (n = to recent studies have that drainage and MAP augmentation can act to enhance spinal cord blood A phase (n = randomized trial and MAP elevation is now underway to the treatment can improve neurological outcomes for patients with acute AIS grade A, B, or C injuries from The study is expected to conclude in The of SCI research is and findings are being with from SCI clinical To achieve in clinical trials in SCI, the of and to In with to level of injury as as ASIA grade have been in of the clinical trials including the cethrin and riluzole The of SCI is likely to the administration of drugs to mitigate the secondary injury at the acute phase, followed by cell transplantation therapy to regenerate damaged spinal cord tissue from subacute to chronic that the therapeutic discussed in this review and the continuous in and clinical research are a to regenerative for SCI. This is by Canadian of Health AOSpine North in and and The support from the in and Regeneration and the is a for and and a for The other have no or in any of the or in this for this

The prognosis for patients with a complete traumatic spinal cord injury (SCI) is generally poor. It is unclear whether some subgroups of patients with a complete traumatic SCI could benefit from early surgical decompression of the spinal cord. The objectives of this study were: (1) to compare the effect of early and late surgical decompression on neurological recovery in complete traumatic SCI and (2) to assess whether the impact of surgical timing is different in patients with cervical or thoracolumbar SCI. A prospective cohort study was followed in a single Level 1 Trauma Center specializing in SCI care. All consecutive patients who sustained a traumatic SCI and were referred between 2010 and 2013 were screened for eligibility. Neurological status was assessed systematically using the American Spinal Injury Association impairment scale (AIS) at arrival to the trauma center and at rehabilitation discharge. Patients operated within 24 h of the trauma were compared with patients operated later than 24 h after the trauma. Potential confounders such as age, Injury Severity Score (ISS), smoking history, body mass index (BMI), Glasgow Coma Scale (GCS) score, and duration of follow-up were recorded. Fifty-three patients with complete SCI were included in the study: 33 thoracolumbar and 20 cervical SCIs. The 38 patients operated <24 h were generally younger than the 15 patients operated ≥ 24 h (p = 0.049). Overall, 28% (15/53) of complete SCI had improvement in AIS: 34% (13/38) who were operated <24 h and 13% (2/15) who were operated ≥ 24 h (p = 0.182). Sixty-four percent (9/14) of cervical complete SCI operated <24 h had improvement in AIS as opposed to none in the subgroup of six complete cervical SCI operated ≥ 24 h (p = 0.008). Surgical decompression within 24 h in complete SCI may optimize neurological recovery, especially in patients with cervical SCI.

Objective: To compare urodynamic findings between patients with complete and incomplete traumatic spinal cord injuries (SCI) and to determine whether it is important to test with urodynamic study in patients with incomplete SCI. Design: Retrospective study Setting: Ankara Physical Medicine and Rehabilitation Training and Research Hospital, Ankara, Turkey Participants: A total of 66 patients with 36 complete and 30 incomplete traumatic SCI were included in the study, from July 2012 to September 2014. Interventions: Urodynamic study Outcome Measures: Maximum cystometric capacity (MCC) , vesicle pressure at MCC, detrusor function (detrusor overactivity or not), bladder complience, bladder storage and emptying disorders, post-void residual volume (PVR) and bladder emptying method were recorded. It was also recorded whether the patients used anticholinergic drugs before urodynamic study. Results: In urodynamic findings MCC, vesicle pressure at MCC, PVR, there was no statistically significant difference between complete and incomplete traumatic SCI patients. Also there was no statistically significant difference in low-compliance of detrusor frequency and bladder storage and emptying disorder frequency. Clean intermittent catheterization (CIC) was the most commonly recommended method after urodynamic studies in both groups of patients with SCI. Conclusions: In urodynamic study findings, there was no statistical difference between complete and incomplete traumatic SCI patients. The present study demonstrate that even if patients with incomplete SCI appear to be functionally better than the patients with complete SCI, urodynamic studies should still be performed in patients with incomplete SCI to identify bladder characteristics and to identify appropriate treatment.

Loss of lower limb motor functions is among the most commonly seen effects of spinal cord injuries (SCI). Even with the current modern medical care, SCI patients require intense care at high expense. Animal models used for research on SCI may help develop better and lower cost therapies. It is well known that neonatal rats with complete SCI are capable of generating autonomous lumbar stepping, some even achieve independent weight support when tested as adults. On the contrary, rats injured at adult ages have limited recovery after a complete spinal cord injury. What can account for the difference? We hypothesized that neonatal and adult SCI animals' muscle synergy patterns were distinguished from each other and from the intacts'. Although sharing a lot of similarity, compared to the adult SCI animals, neonatal SCI animals had less synergies merging. Some xiv individual synergies of the neonatal SCIs' might resemble the intact animals more than adult SCIs'. To test the hypothesis, we examined the muscle synergy pattern using locomotor electromyography (EMG) in adult animals injured as neonates (T9/10 complete SCI, n=9), intact adult rats (n=12) and the same adult rats 10~14 days after T9/10 complete SCI (n=9). We found that adult SCI animals' synergies tended to merge post injury compared to the intact animals. The intacts also deviated from the neonatal and adult SCI animals regarding the correlation of all the synergies and individual synergy to a common synergy template. While sharing some similarity, in some individual synergies' correlation values to the common template, the neonatal animals were more similar to the adult SCIs shortly after injury than to the intacts. The neonatal synergies appeared to be preserved into adulthood and revealed after adult SCI. If given systematical training, would the synergies of adult SCI animals change with function? And if they do, would the change be the same regardless of the rehabilitation paradigms and recovery outcome? In order to answer these questions, we studied the synergy changes following robot-driven epidural stimulation combined with treadmill training (ES) and robotic assisted treadmill only (TM) systematic long-term training and we compared these to the animals resting in the cage after complete adult SCI. We hypothesized that synergies would tend to merge right after injury. As time went by after injury, the synergies' spatial structure would be simplified. However, with successful rehabilitation, the further merging and simplification of the synergies were avoided. To investigate the only (TM) systematic long-term training and we compared these to the animals resting in the cage after complete adult SCI. We hypothesized that synergies would tend to merge right after injury. As time went by after injury, the synergies' spatial structure would be simplified. However, with successful rehabilitation, the further merging and simplification of the synergies were avoided. To investigate the synergies' relationship to therapeutic methods and efficacy, we trained three groups of animals with ES training, TM training and in cage resting respectively. We examined their synergies through 8 weeks' rehabilitation period. ES and TM training showed beneficial effects on recovery after SCI. Synergy changes were linked with functional locomotion recovery. Unlike cage resting, the effective training harnessed and separated the synergies merging post injury and each synergy ended with more refined spatial patterns. However, although both ES and TM helped SCI animals recovered successfully, their underlying neural mechanisms were not the same in terms of synergy changes. Our study suggested that the TM training likely did not reverse the merging process to the extent that the ES training did.

Urodynamics is the gold standard for evaluating the function of neurogenic bladder after spinal cord injury (SCI), but there are few studies on urodynamics in patients with complete and incomplete suprasacral SCI in different periods.There is a lack of sufficient evidence for the timing of the first urodynamic examination. The urodynamic results of 101 patients with complete and incomplete suprasacral SCI at 0-30, 31-60, 61-90, and 91-365 days after injury were included. Urodynamic parameters were compared between 0-90 and 91-365 days, including detrusor overactivity (DO), bladder compliance (BC), bladder-filling sensation, maximum cystometric capacity (MCC), detrusor external sphincter dyssynergia (DESD), maximum urinary flow rate (Qmax), detrusor pressure at a maximum urinary flow rate (PdetQmax). There were 45 patients with complete SCI and 56 with incomplete SCI. With the course's prolongation, the proportion of DO increased gradually in patients with complete and incomplete injury within 90 days, while the MCC gradually decreased. The bladder-filling sensation of patients with complete SCI is mostly absent. Significant differences were found between 0-90 and 91-365 days in terms of DO, DESD, MCC, Qmax, and PdetQmax incomplete SCI, and DESD in incomplete SCI, and between complete and incomplete SCI in terms of DO, bladder filling sensation, MCC, Qmax, PdetQmax at 0-90 days after injury, and bladder filling sensation at 91-365 days after injury. Urodynamic examination should be conducted as soon as possible after injury in patients with incomplete suprasacral SCI, while for those with complete injury, the urodynamic examination can be initiated following clinical symptoms within 90 days after injury.

Analysis of Delays to Surgery for Cervical Spinal Cord Injuries

A retrospective study of surgically treated patients with cervical spinal cord injury (SCI) from the National Trauma Data Bank Research Data Set. To determine how time to surgery differs between SCI subtypes, where delays before surgery occur, and what factors are associated with delays. Studies have shown that patients with cervical SCI undergoing surgery within 24 hours after injury have superior neurological outcomes to patients undergoing later surgery, with most evidence coming from the incomplete SCI subpopulation. Surgically treated patients with cervical SCI from 2011 and 2012 were identified in National Trauma Data Bank Research Data Set and divided into subpopulations of complete, central, and other incomplete SCIs. Relationships between surgical timing and patient and injury characteristics were analyzed using multivariate regression. A total of 2636 patients with cervical SCI were identified: 803 with complete SCI, 950 with incomplete SCI, and 883 with central SCI. The average time to surgery was 51.1 hours for patients with complete SCI, 55.3 hours for patients with incomplete SCI, and 83.1 hours for patients with central SCI. Only 44% of patients with SCI underwent surgery within the first 24 hours after injury, including only 49% of patients with incomplete SCI.The vast majority of time between injury and surgery was after admission, rather than in the emergency department or in the field. Upper cervical SCIs and greater Charlson Comorbidity Index were associated with later surgery in all 3 SCI subpopulations. The majority of patients with SCI do not undergo surgery within the first 24 hours after injury, and the majority of delays occur after inpatient admission. Factors associated with these delays highlight areas of focus for expediting care in these patient populations. 4.

Canadian Spine SocietyPresentation CPSS1: Spinal insufficiency fracture in the geriatric pediatric spinePresentation CPSS2: The clinical significance of tether breakages in anterior vertebral body growth modulation: a 2-year postoperative analysisPresentation CPSS3: Anterior vertebral body growth modulation for idiopathic scoliosis: early, mid-term and late complicationsPresentation CPSS4: Ovine model of congenital chest wall and spine deformity with alterations of respiratory mechanics: follow-up from

Pressure ulcers (PUs) are common complications in patients with complete spinal cord injury (SCI) or incomplete SCI in which sensory function is spared. Most studies analyzing associated factors of PU and SCI have been performed in cases of traumatic SCI and in just a few cases of nontraumatic SCI. This study was designed to look specifically at the differences in causative factors of PU in cases of traumatic and nontraumatic SCIs. The authors performed a retrospective, cross-sectional study evaluating patients with complete and incomplete SCIs (American Spinal Injury Association Grades A and B) under the coverage of the financial, medicosocial, and rehabilitative support provided by the State Welfare Organization of Iran (SWOI). There were 3791 cases of traumatic SCI (63.2%) and 2110 cases of nontraumatic SCI (35.2%). For 94 patients (1.6%), sufficient data were not available. A PU was detected in 39.2% of all patients with an SCI (71.8% of those with traumatic SCI vs 28.2% of those with nontraumatic SCI). A univariate analysis showed a significant association between occupation, education, and the presence of PU in patients with a traumatic SCI (p < 0.05). This contrasted with nontraumatic SCI in which an association between PU and age was noted (p < 0.05). Using logistic regression, traumatic cause, older age, an interval less than 1 year since the onset of SCI, male sex, and single status were found to significantly increase the risk of PU in all patients with an SCI. However, a higher education level had a preventive effect on PU. This study revealed some risk factors for PU in the authors' setting. The authors' findings suggest a possible difference between the risk factors for PU in patients with both types of SCI. Further study on the pathoetiology of these differences is paramount in the future.

Neurorehabilitation and Neuroprosthetic Technologies to Regain Motor Function Following Spinal Cord Injury

Reorganization of spinal neural circuitry and functional recovery after spinal cord injury

Cross-sectional study. To compare exercise-related self-perceptions in persons with complete and incomplete spinal cord injury (SCI) and to identify factors that explain the variance of perceived exercise mastery in the study population. Sunnaas Rehabilitation Hospital and the Norwegian School of Sport Sciences, Norway. A total of 116 respondents (47 persons with complete and 69 persons with incomplete SCI) answered a questionnaire measuring self-rated physical exercise habits and self-perceptions in exercise. Respondents with complete SCI performed a max test on an arm ergometer. Exercisers with complete SCI reported a significantly higher perceived exercise mastery (P=0.002) and exercisers with incomplete SCI reported a significantly lower perceived exercise mastery (P=0.012) than nonexercisers. Exercisers in both groups reported a higher perceived fitness (complete SCI, P=0.016; incomplete SCI, P=0.004) than nonexercisers. A regression analysis showed that exercising versus nonexercising (exercise status) was the only variable that contributed to the variance in perceived exercise mastery for persons with complete SCI (P<0.001). For persons with incomplete injury, exercise status and exercise hours per week contributed to the variance in perceived exercise mastery. Although perceived fitness is associated with exercise in the whole SCI population, perception of exercise mastery is negatively related to exercise in persons with incomplete SCI, in contrast to those with complete lesions.

Management of Mental Health Disorders, Substance Use Disorders, and Suicide in Adults with Spinal Cord Injury: Clinical Practice Guideline for Healthcare Providers.

Introduction The spinal trauma (ST) presents 82.8% in men around 32 years' old; the 56.5% has spinal cord injury (SCI), whose word incidence is 25.5 million/year. The main cause is traffic accidents. In Colombia, 55% of ST are cervical and 45% has complete SCI. Overall, 80 to 85% are men between 20 to 30 years' old and 25% is related to alcohol consumption. The American Spinal Injury Association (ASIA) classifies the SCI in: (1) complete sensitive and motor function; (2) incomplete: normal sensibility, no motor function (MF); (3) incomplete: MF under the lesson less than 3/5; (4) incomplete: MF more than 3/5; and (5) normal. Spine divides itself in upper cervical: C0–C2 (UCS), low cervical C3–C7 (LCS), thoracic, and lumbar. Objectives This study aims to classify the ST according its place, SCI, and surgical treatment. This study also characterizes the population under surgery by ST; establish its level, describe the SCI associated with ST, and stablish the surgical treatment according the level of the ST. Patients and Methods Retrospective, analytic, and descriptive study, using the clinical registers. Patients were admitted in the emergency of “Clínica de la Unidad de la Sabana” (CUS). Both sexes, no age limit age, between January 2009 and July 2014, who suffered spine arthrodesis caused by ST. Those who did not need surgery were excluded. The collection data form included the following: identification number, age, sex, level of the ST, SCI according ASIA scale, and surgical treatment. The data were analyzed in a descriptive and comparative way. Results The population comprised of 60 patients, 46 men and 14 women. The more frequent age was the second decade of life (17 patients, 11 M:6 W), followed by the third one (14 patients, 11 M:3 F). The principal segment affected was the cervical (24 patients: 5 UCS and 19 LCS), followed by lumbar (22 patients). The most frequent place was L1 (13) and C6–C7 (10). There were 29 patients with SCI ASIA A, 10 with ASIA E, and 21 patients with incomplete SCI. The lesions in the UCS did not have SCI; in the LCS were 15 ASIA A, 2 in ASIA E, and 2 incomplete SCI; thoracic had 10 ASIA A, 1 ASIA E, and 3 incomplete SCI, lumbar had 4 ASIA A, 2 ASIA E, and 16 incomplete SCI. The surgeries performed in the UCS were one 360 degrees arthrodesis, four posterior arthrodesis (PA), LCS: 6 corpectomy, 13 PA; thoracic and lumbar: 14 and 22 PA, respectively. Conclusion In our study, 76.6% were male patients, 51.6% were between the second and the third decade of life, as reported in the literature. Overall, 40% of the ST was cervical, a little lower than reported nationally, 48.33% had SCI ASIA A, very similar to the word statistics. The relation of the ST and SCI reported that the group with the highest SCI ASIA A was the LCS (78.94%) and thoracic (71.4%), the incomplete SCI was more frequent in the lumbar spine (72.7%), and the UCS has no SCI. The most frequent surgical approach was the posterior, in 88.3% of patients.

Context The main rehabilitation goals for patients with a spinal cord injury (SCI) are to reduce disability, limit impairment, and regain walking ability. Many prognostic factors affect the recovery and ambulation capacity of patients. After SCI, muscles below the lesion level change morphologically. Objective As the muscle thickness is a significant factor for identifying muscle strength, joint functions and joint torque, the aim of this study was to compare piriformis muscle (PM) maximum thickness in patients with incomplete SCI, with those of a sex, age, weight and height-matched control group. Maximum PM thickness was also compared between cases of incomplete and complete SCI in order to estimate whether spasticity and ambulatory status influence PM thickness after incomplete chronic SCI. Methods The demographic data, injury characteristics, and clinical findings were recorded for each patient. Muscle thickness was measured using ultrasonography and relationships between PM thickness and demographic and clinical findings were analyzed and compared between the groups. Results The PM thickness of SCI patients was determined to be significantly lower than that of the healthy control subjects. No significant differences were observed in the comparisons of other values between patients with incomplete SCI and the control group. Conclusion Significant muscle atrophy of the PM is seen in SCI. There is a need for further investigation of the relationship between muscle size and function, and physiological deficits in skeletal muscle and functional ability after SCI.