Self-reported communication and swallowing difficulties in people following spinal cord injury in New Zealand

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

Background/Objective: Cardiovascular abnormalities and arrhythmias are common in individuals with spinal cord injury (SCI) who are undergoing vibrostimulation for sperm retrieval. The study aimed to examine cardiovascular control in men with SCI undergoing this procedure.Methods: Individuals with chronic cervical (n = 8; age: 33.1 ± 1.9 years) and upper thoracic SCI (n = 5; age: 35.2 ± 2.9 years) volunteered for vibrostimulation, with continuous blood pressure (Finometer) and electrocardiographic monitoring. Patients were characterized further by sympathetic skin responses (SSR) to assess descending autonomic spinal pathways and American Spinal Injury Association (ASIA) scores to assess motor and sensory pathways.Results: All but one subject with cervical SCI were ASIA A or B and were negative for SSR in the hands and feet. All subjects with upper thoracic SCI were ASIA A or B and were positive for SSR in the hands. Systolic blood pressure was lower in men with cervical injury at rest. Vibrostimulation induced an increase in systolic blood pressure >20 mmHg in all patients with cervical SCI (range = 125/65-280/152; median = 167/143 mmHg) and in 2 thoracic subjects (151/104 and 170/121 mmHg). During ejaculation, 6 cervical and 3 thoracic subjects developed arrhythmias (5 with bradycardia, 6 with premature atrial contractions, 4 with ventricular excitation, 1 with junctional rhythm, and 1 with heart block).Conclusion: The vibrostimulation procedure induced electrocardiographic abnormalities and autonomic dysreflexia in subjects with either cervical or high thoracic SCI.

OBJECTIVEConventional MRI is routinely used to demonstrate the anatomical site of spinal cord injury (SCI). However, quantitative and qualitative imaging parameters have limited use in predicting neurological outcomes. Currently, there are no reliable neuroimaging biomarkers to predict short- and long-term outcome after SCI.METHODSA prospective cohort of 23 patients with SCI (19 with cervical SCI [CSCI] and 4 with thoracic SCI [TSCI]) treated between 2007 and 2014 was included in the study. The American Spinal Injury Association (ASIA) score was determined at the time of arrival and at 1-year follow-up. Only 15 patients (12 with CSCI and 3 with TSCI) had 1-year follow-up. Whole-cord fractional anisotropy (FA) was determined at C1-2, following which C1-2 was divided into upper, middle, and lower segments and the corresponding FA value at each of these segments was calculated. Correlation analysis was performed between FA and ASIA score at time of arrival and 1-year follow-up.RESULTSCorrelation analysis showed a positive but nonsignificant correlation (p = 0.095) between FA and ASIA score for all patients (CSCI and TCSI) at the time of arrival. Additional regression analysis consisting of only patients with CSCI showed a significant correlation (p = 0.008) between FA and ASIA score at time of arrival as well as at 1-year follow-up (p = 0.025). Furthermore, in case of patients with CSCI, a significant correlation between FA value at each of the segments (upper, middle, and lower) of C1-2 and ASIA score at time of arrival was found (p = 0.017, p = 0.015, and p = 0.002, respectively).CONCLUSIONSIn patients with CSCI, the measurement of diffusion anisotropy of the high cervical cord (C1-2) correlates significantly with injury severity and long-term follow-up. However, this correlation is not seen in patients with TSCI. Therefore, FA can be used as an imaging biomarker for evaluating neural injury and monitoring recovery in patients with CSCI.

Objective To compare and analyze the clinical characteristics of acute central cervical spinal cord injury with only upper extremity involvement and with both upper and lower extremity involvement. Methods A retrospective case control study was made on clinical data of 76 patients with acute central cervical spinal cord injury hospitalized from January 2010 to December 2013. Nerve injury involved was only upper extremity in 39 patients (upper extremity group), but both upper and lower extremities in 37 patients (upper-and lower-extremity group). In upper extremity group, there were 35 males and four females, age was 21-80 years [(52.5±13.4)years], injury resulted from traffic accidents in 24 patients, ground-level falls in eight, high-level falls in six and heavy-object hit in one, and level of injury was C3/4in 16 patients, C4/5in 14 and C5/6in nine. In upper- and lower-extremity group, there were 30 males and seven females, age was 36-78 years [(59.6±9.7)years], injury resulted from traffic accidents in 16 patients, ground-level falls in 11, high-level falls in seven and heavy-object hit in three, and level of injury was C3/4in nine patients, C4/5in 18 and C5/6in 10. Sagittal diameter of the cervical spinal canal, maximal canal compromise, maximal spinal cord compression, degenerating factors of the cervical spine and treatment protocols were determined. Upper extremity function was assessed with the American spinal injury association (ASIA) score. Results There were significant differences between upper extremity group and upper- and lower-extremity group in sagittal diameter of the cervical spinal canal [(7.5±1.5)mm ∶(6.8±1.2)mm], maximal canal compromise [(28.9±9.6)% ∶(34.9±10.6)%], ASIA score at admission[(31.6±11.8)points ∶(22.7±11.3)points)] and ASIA score at last follow-up [(46.2±4.2)points ∶(40.2±4.0)points](P 0.05). Lower prevalence of posterior osteophyte of the vertebral body was noted in upper extremity group than upper- and lower-extremity group (15% ∶51%) (P<0.01). Twenty patients (49%) in upper extremity group were surgically treated, while 31 patients (84%) in upper-and lower-extremity group (P<0.05). Conclusions Compared to acute central cervical spinal cord injury with both upper and lower extremity involvement, the injury with only upper extremity involvement is much common in younger patients and is characterized by lowered frequency of osteophyte, large buffer space, mild nerve damage, preferred non-operation treatment and good prognosis. Key words: Spinal cord injuries; Magnetic resonance imaging; Neurological status

ObjectiveThe purpose of this study was to investigate the effects of the number of fused segments, the timing of surgery and their interaction on the prognosis of patients with cervical spinal cord injury without fracture and dislocation (CSCIWFD), and to determine the appropriate time restrictions for early surgery in CSCIWFD patients based on the current diagnosis and treatment system in southern China.MethodsCSCIWFD patients who underwent anterior cervical decompression and internal fusion (ACDF) from January 2012 to June 2017 were selected. The patients were grouped according to the timing of surgery and the number of fused segments and evaluated based on their American Spinal Injury Association (ASIA) score, ASIA impairment scale, and Japanese Orthopaedic Association (JOA) score before and after surgery. SPSS22.0 software was used for the statistical analysis.ResultsThe ASIA score, JOA score, and ASIA impairment scale in all follow-ups were significantly higher than before surgery (p < 0.05). The ASIA and JOA scores at 6, 12, and 24 months after surgery of the patients who underwent ACDF within 72 h were significantly better than those of the patients who underwent ACDF after 72 h (p < 0.05). There were significant differences in postoperative ASIA and JOA scores at 12 and 24 months between the short-segment and three-segment fusion groups (p < 0.05). The results of the interaction between the surgical timing and the number of the fused segments showed that the postoperative ASIA and JOA scores at 6, 12, and 24 months were significantly higher in the patients who underwent early short-segment fusion than in those who underwent delayed short-segment fusion (p < 0.05). However, no statistically significant difference was found between early and delayed surgery in the patients who underwent three-segment fusion (p > 0.05).ConclusionACDF is safe and effective for the treatment of CSCIWFD. For patients with single- or double-segment injury, early (within 72 h) ACDF is associated with a more satisfactory prognosis. Due to the limitation of the small sample size, we cautiously recommend that 72 h can be used as a time limit for early surgery for CSCIWFD patients in regions where earlier surgery cannot be provided by the current diagnosis and treatment system.

Objective To explore the factors influencing the functional recovery of patients with spinal cord injury (SCI) at discharge. Methods A total of 105 patients with SCI admitted to the rehabilitation medicine department at Huashan Hospital between December 2004 and October 2009 were studied. Data on eleven variables were collected including the patients' medical history, physical examination results and American Spinal Injury Association (ASIA) scores at admission. Functional status was registered according to the modified Barthel index (MBI) assessed at admission and before discharge. Linear regression analysis was used to assess the influence of the variables.Results After rehabilitation, average MBI and ASIA scores were significantly higher. The multiple regression analysis revealed that injury grade, motor and pinprick sensation scores at admission were related to MBI before discharge.The duration of rehabilitation, the rehabilitation treatment course and motor scores at admission were related to MBI increases during hospitalization. Conclusions Patients with different ages, injury levels and severity can improve their functional abilities through rehabilitation treatment, especially patients with better initial motor ability, longer treatment and earlier intervention. Key words: Spinal cord injury; Activities of daily living

State of the Science Conference in Spinal Cord Injury Rehabilitation 2011: introduction

To investigate the safety and therapeutic efficacy of autologous olfactory ensheathing cell (OEC) transplantation in cervical spinal cord injury (SCI). Patients with cervical SCI of >6 months' duration were treated with autologous OECs, injected into the area surrounding the SCI under magnetic resonance imaging guidance, twice a week for 4 weeks. Patients were evaluated before treatment and at 3, 6, 12 and 24 months post-treatment, using the American Spinal Injury Association (ASIA) Impairment Scale, the ASIA sensory and motor score and the Functional Independence Measure (FIM) score. Eight patients were recruited to the study. Three months after treatment, ASIA and FIM scores had improved significantly compared with pretreatment, though by 1 year no further significant improvements in the ASIA score were seen. The return of substantial sensation and motor activity in various muscles below the injury level was observed in three patients during follow-up. In addition, bladder function was restored in two patients. There were no serious complications postoperatively or during the follow-up period. This study provides preliminary evidence of the safety and possible efficacy of autologous OEC transplantation.

Objective To evaluate the clinical efficacy of mouse nerve growth factor (mNGF) plus mecobalamin in the treatment of incomplete spinal cord injury (ISCI) without high-dose methylprednisolone therapy. Methods From October 2007 to September 2010,72 ISCI patients (Frankel grades B,C & D)without previous high-dose methylprednisolone therapy were treated in our department,of whom 56 were retrospectively selected for the present study and divided into 2 groups.In group A 28 patients were treated with combination of mNGF and meeobalamin; 28 patients in group B were treated with mecobalamin only.In this series,American Spinal Injury Association (ASIA) impairment scale and Activity of Daily Living (ADL) evaluation were used to observe and calculate nerve function improvement preoperation and 1 week,8 weeks,12 months postoperation. Results The mean follow-up period was 20 months (from 12 to 48 months).No mortality or incision infection was observed.Fusions of bone graft were observed 10 months postoperation on average.The ASIA and ADL scores at 1 week,8 weeks and 12 months postoperation were significant higher than those preoperation in both groups (P ＜0.05) except the ASIA score 1 week postoperation in group B.The postoperative ASIA and ADL scores in Group A were all significantly higher than those in group B ( P ＜ 0.05).The nerve function improvement at 1 week,8 weeks and 12 months postoperation in group A were 32.1％ (9/28),82.1％ (23/28) and 92.9％ (26/28) respectively,which were better than those in group B [25.0％ (7/28),50.0％ (14/28) and 71.4％ (20/28) ],with a significant difference at 8 weeks and 12 months postoperation ( P ＜ 0.05 ). Conclusion Compared with administration of sole mecobalamin,combination of mNGF and mecobalamin proves to be highly effective in promoting ISCI recovery and improving nerve functiont. Key words: Spinal cord injury; Mouse; Nerve growth factor; Mecobalamin; Nerve function

Objective To investigate the characteristics and treatment effects in patients with spinal fractures associated with dural tears. Methods A retrospective analysis was made on 185 patients with spinal fractures presenting to hospital from February 2013 to February 2015. There were 103 males and 82 females, aged 17-73 years (mean, 58 years). Causes of injury were high falls in 72 patients , traffic collisions in 58, hitting by heavy objects in 41, ground-level falls in 12, and collision events in two. Cervical spine fractures were seen in 65 patients, thoracic vertebra fractures in 51, and lumbosacral vertebral fractures 69. Neurologic deficit was assessed using the American Spinal Injury Association (ASIA) score, including grade A in 24 patients, grade B in 22, grade C in 26, grade D in 37 and grade E in 76. Eighty patients were managed by simply anterior surgery, 97 by posterior surgery, and eight by anterior-posterior surgery. Twenty-one patients were found with dural tears (group A) and 164 patients without dural tears (group B). Incidence of dural tears in cervical, thoracic and lumbosacral vertebral fractures were recorded and compared. Preoperative neurologic deficit, laminar fracture and spinal canal encroachment rate were compared between groups. Neurological function and complications associated with dural repair were detected. Results In group A, ten patients were rated ASIA grade A, five grade B, three grade C, one grade D and two grade E. In group B, 14 patients were rated ASIA grade A, 17 grade B, 23 grade C, 36 grade D and 74 grade E. Group A accounted for 11%(7/65) of cervical, 10%(5/51) of thoracic, and 13%(9/69)of lumbosacral spine fractures (P>0.05). Nineteen patients (91%) in group A were complicated with neurological deficit, compared to ninety patients (54.9%) in group B (P<0.01). Eighteen patients (86%) in group A had laminar fractures, compared to fifteen patients (9.1%) in group B (P<0.01). In group A, rate of spinal canal encroachment was (62.3±12.1)% and 17 patients (81%) showed spinal canal encroachment of greater than 50%. While in group B, rate of spinal canal encroachment was (36.2±15.6)% and 25 patients (15.2%) showed spinal canal encroachment of greater than 50% (P<0.01). For dural tears in group A, 11 patients were treated by direct suturing, four by thoracolumbar fascia repair, three by artificial dural coverage and three by fibrin glue sealing. In group A, 19 patients were followed up and one of them presented persistent cerebral spinal fluid leak that necessitated an irrigation and debridement to cure. ASIA score was improved from grade A to B in two patients, grade B to C in one, grade C to D in one and grade D to E in one at the final follow-up. Conclusions Majority patients with spinal fractures associated with dural tears exist severe neurologic deficit, spinal canal encroachment and laminar fractures. Incidence of dural tear in cervical, thoracic and lumbosacral vertebral fractures is similar. Incidence of complications related to dural tear repair is low, but the neurological function recovery is poor after operation. Key words: Spinal fractures; Dura mater; Spinal cord injuries; Complications

Individuals with spinal cord injury (SCI) are prone to orthostatic hypotension (OH). We aimed to develop a simple bedside test to evaluate autonomic control following chronic SCI, and to identify those most at risk of OH and cardiovascular dysfunction. We studied 14 subjects with cervical SCI, 11 with thoracic SCI, and 17 able-bodied controls. We continuously recorded heart rate (HR; ECG) and beat-to-beat systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures (Finometer) while supine, and following the passive assumption of an upright seated position. Stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were calculated. Plasma catecholamines were determined. Motor and sensory loss was assessed using the American Spinal Injury Association (ASIA) impairment scale. Autonomic pathways were assessed from sympathetic skin responses (SSR). Cervical SCI subjects had lower supine HR, SAP, and noradrenaline levels than thoracic SCI and controls (p < 0.05), and lower DAP and MAP than controls (p < 0.05). When upright, HR increased in all groups (p < 0.05); SAP, DAP, and MAP increased (p < 0.01) in thoracic SCI and controls, but not in cervical SCI. Cervical SCI had larger postural falls in SV (p < 0.05) and CO, with smaller increases in TPR than the other two groups. Upright catecholamine levels were lower in cervical SCI (p < 0.05) than thoracic SCI and controls. Completeness of SCI assessed by ASIA scale did not necessarily correlate with autonomic completeness assessed by SSR. Cardiovascular control during orthostasis was impaired and OH was common in cervical SCI, but not thoracic SCI. SSR may identify those at greatest risk of orthostatic hypotension and impaired cardiovascular control. We advocate that assessments of autonomic function be included in the neurological evaluation of SCI, in addition to the ASIA assessment.

Introduction to the Guidelines for the Management of Acute Cervical Spine and Spinal Cord Injuries

The strong correlation between evoked potentials (EPs) and American Spinal Injury Association (ASIA) scores in individuals with spinal cord injury (SCI) suggests that EPs may serve as reliable predictive markers for rehabilitation progress. Numerous studies have confirmed a relationship between variations in somatosensory evoked potentials (SSEPs) and ASIA scores, especially in the early stages of SCI. Machine learning’s (ML’s) increasing importance in medicine is driven by the growing availability of health data and improved algorithms. It enables the creation of predictive models for disease diagnosis, progression prediction, personalized treatment, and improved healthcare efficiency. Data-driven approaches can significantly improve patient care, reduce costs, and facilitate personalized medicine. The meticulous analysis of medical data is crucial for timely disease identification, leading to effective symptom management and appropriate treatment. This study applies artificial intelligence to identify predictors of SCI progression, as measured by the disability index, ASIA impairment scale (AIS), and final motor recovery. We aim to clarify the prognostic role of electrophysiological testing (SSEPs, MEPs, and nerve conduction studies (NCSs)) in SCI. We analyzed data from a medical database of 123 records. We developed an ML-based intelligent system, utilizing ensemble algorithms combining decision trees and neural network approaches, to predict SCI recovery. Our evaluation showed SEP accuracies of 90% for motor recovery prediction and 80% for AIS scale determination, comparable to full electrophysiology evaluation accuracies of 93% and 89%, respectively, and generally superior results compared to MEP and NCS results. EPs emerged as the best predictors, comparable to a comprehensive electrophysiology assessment, significantly improving accuracy compared to clinical findings alone. An electrophysiological assessment, when available, increased overall accuracy for final motor recovery prediction to 93% (from a maximum of 75%) and, for ASIA score determination, to 89% (from a maximum of 66%). Further validation is needed with a larger dataset. Future research should validate that sensory electrophysiology assessment is a less expensive, portable, and simpler alternative to other prognostic tests and more effective than clinical assessments, like the AIS, biomarker for SCI, and personalized rehabilitation planning.

Patients with cervical spine injury may require both anterior cervical spine fusion and tracheostomy, particularly in the setting of associated cervical spinal cord injury (SCI). Despite the close proximity of the two surgical incisions, we postulated that tracheostomy could be safely performed after anterior spine fixation. In addition, we postulated that the severity of motor deficits in patients with cervical spine injury would correlate with the need for tracheostomy. A retrospective review was undertaken of all adult trauma patients diagnosed with cervical spine fractures or cervical SCI admitted between June 1996 and June 2001 at our university Level I trauma center. Demographic data, severity of neurologic injury based on the classification of the American Spinal Injury Association (ASIA), complications, and use and type of tracheostomy were collected. In the subgroup of patients with unstable cervical spine injury that underwent anterior stabilization and tracheostomy, data regarding timing and technique of these procedures and wound outcomes were also collected. Categorical data were analyzed using chi analysis using Yates correction when appropriate, with p <0.05 considered significant. During this time period, 275 adult survivors were diagnosed with cervical spinal cord or bony injury. Forty-five percent of patients with SCI (27 of 60) and 14% of patients without SCI (30 of 215) underwent tracheostomy (p <0.001). Moreover, on the basis of the ASIA classification system, 76% of ASIA A and B patients, 38% of ASIA C patients, 23% of ASIA D patients, and 14% of ASIA E patients were treated with tracheostomy (p <0.001). In the subgroup that underwent both anterior spine fixation and tracheostomy (n=17), the median time interval from spine fixation to airway placement was 7 days (interquartile range, 6-10 days), with 71% of these tracheostomies performed percutaneously. No patient developed a wound infection or nonunion as a consequence of tracheostomy placement, and there were no deaths because of complications of either procedure. These data support the safety of tracheostomy insertion 6 to 10 days after anterior cervical spine fixation, particularly in the presence of cervical SCI. The presence of severe motor neurologic deficits was strongly associated with the use of tracheostomy in patients with cervical spine injury. Percutaneous tracheostomy, which is our technique of choice, may be advantageous in this setting by virtue of creating only a small wound. The optimal timing and use of tracheostomy in patients with cervical spine injury requires further study.

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.