Introduction: We previously classified serum oxidative stress marker levels in patients with acutely worsening compression myelopathy (AM) as severe. These oxidative stress markers may influence neurological recovery after surgery for AM (BMC Musculoskelet Disord, 2019). We hypothesized that the oxidative stress is decreased by surgical treatment. Therefore, we conducted an observational study to determine the time course changes of serum oxidative stress marker in patients with cervical compression myelopathy after surgery.
Methods: In the present study, we included 40 patients who underwent surgery at our hospital to treat acutely worsening compression myelopathy (AM; n=21) and chronic compression myelopathy (CM; n=19) between April 2015 and October 2018. Serum samples were collected at the time of hematological examinations before surgery and the postoperative follow-up at 3 months, 6 months, and 1 year after surgery. Oxidative stress levels were determined by measuring reactive oxygen metabolites (ROM) that reflect serum hydrogen peroxide levels. A normal ROM level in healthy controls is <300 (U. CARR), whereas levels of >340 and >400 are defined as moderate and severe oxidative stress, respectively. Neurological evaluations using a Japanese Orthopaedic Association (JOA) score for cervical myelopathy were performed and the correlation between ROM and recovery rate of JOA score was also investigated.
Results: ROM levels (U. CARR) in AM increased from 407.6±74.3 before surgery to 428.0±94.9 at 3 months after surgery and ROM levels in CM increased from 357.5±74.8 to 379.6±54.9 indicating a significant increase at 3 months after surgery equally in both groups (p<0.05) despite the favorable neurological improvement observed in both groups. By contrast, ROM gradually decreased until 1 year follow-up in both groups. There was no correlation between the changes of ROM and the recovery rate of JOA scores. In 3 patients with cases complicated by C5 palsy, ROM levels increased from 460.7±86.0 before surgery to 519.3±131.6 at 3 months after surgery and were significantly higher than those in other cases (p<0.05), and the high ROM levels were maintained until 1 year follow-up.
Conclusions
Serum oxidative stress markers in compression myelopathy did not decrease but were increased at 3 months after surgery despite the favorable neurological improvement observed. Serum oxidative stress markers were higher and remained elevated in cases complicated with C5 palsy.

【Background】
Elderly people often develop severe cervical spinal cord injury with relatively low-energy trauma, which is attributed to their high incidence of cervical spondylosis and consequent canal stenosis. The patients with AIS A cervical spinal cord injury have been considered to have a low likelihood of neurological recovery. However, several recent reports indicated favorable neurological outcome of the patients who underwent decompression surgery of the cord within 24 hours of the injury. The objective of the study is to clarify the characteristics of the patients who are likely to benefit from the early decompression surgery.
【Methods】
Among 108 patients treated for cervical spinal cord injury in our trauma center between 2015 and 2019, 83 were initially evaluated as AIS A, 82 underwent decompression surgery of the cord within 24 hours of the injury and 80 survived. We evaluated association between characteristics of the 80 survived patients and their neurological outcome employing the ordinal logistic regression model. We evaluated the outcome by AIS at discharge and assigned it as a response variable. We also assigned age, sex, interval between the injury and the surgery, radiological evidence of cervical spine fracture and that of dislocation as explanatory variables.
【Results】
Among the 80 patients, median [IQR] of age and the interval were 66.5[50-75] y.o. and 385[300-508.8] min, 72 were male, the major fracture was radiologically evident in 26 and dislocation in 21. AIS at discharge were A:33, B:17, C:25 and D:5. The model indicated older age (OR 1.024[95%CI 1.0003-1.050] ), interval between the injury and the surgery (1.004[1.002-1.007]) and absence of the fracture (3.03[1.26-7.72]) as significant independent predictors of favorable neurological outcome.
【Conclusion】
Almost 60% of the patients with AIS A cervical spinal cord injury showed neurological recovery after decompression surgery of the spinal cord within 24 hours of the injury. This result confirmed efficacy of the early decompression of spinal cord to enhance the recovery by preventing the secondary injury. The ordinal logistic regression analysis indicated that elderly patients without evident fracture or dislocation were more likely to benefit from the early decompression. As elderly patients with severe spinal cord injury are considered to be at high risk of complications and mortality, usually the conservative treatment avoiding the acute phase surgery is preferred. In contrast, together with relatively low post-operative in-hospital mortality (2.5%) of the patients, our results indicated that elderly patients traumatized in relatively low-energy trauma are the candidates for the early decompression surgery at earliest possible timing.

Introduction: MLC601/MLC901 (NeuroAiD) are natural product formulations shown to be safe and to aid recovery after neurological injuries, particularly stroke and traumatic brain injury. MLC601/MLC901 may, likewise, have a role in enhancing recovery after spinal cord injury (SCI), a devastating condition with limited therapeutic options. This ongoing pilot study aims to assess the safety and efficacy of NeuroAiD among subjects who sustained moderately-severe to severe SCI.

Methods: This prospective cohort study (ClinicalTrials.gov Identifier: NCT02537899) included subjects with moderately-severe to severe SCI, defined as American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade A or B. Subjects received open-label MLC601/MLC901 for 6 months in addition to standard care and followed for 24 months.

Anonymised data were collected at baseline and months (M) 1, 3, 6, 12, 18, and 24. The online registry recorded safety data and the following outcome measures: AIS grade, Short Form (SF-8) Health Survey, and Spinal Cord Injury Independent Measure (SCIM). Data were analysed using the Last Observation Carried Forward method.

Results: This analysis included 29 subjects out of the recruitment target set at 30. Median age was 36 years (range 17 – 73), with 5 (17%) female. The level of SCI was cervical in 41% and thoracic in 59%. The most common mechanisms of injury were road traffic accident (45%) and fall (31%).

For the co-primary endpoint of AIS grade at M6, data were available for 27 subjects. At baseline, 20 (69%) were AIS grade A and 9 (31%) were AIS grade B. By M6, 11 (41%) converted to a better grade.

M6 outcome was analysed for each baseline AIS grade. Among subjects with baseline AIS grade A, 6 (33%) converted to grade B or better. Among subjects with baseline AIS grade B, 5 (56%) improved to grade C or better, with 1 subject achieving full recovery (AIS grade E), while 1 subject worsened to grade A. No other adverse events were reported. There were 6 deaths, 5 (83%) were AIS grade A at baseline. All deaths occurred prior to M6 evaluation; none were considered related to NeuroAiD.

Conclusions: MLC601/MLC901 shows remarkable promise as a safe adjunctive therapy for aiding recovery in our cohort of subjects with moderately-severe to severe SCI, compared to published outcomes.

Background
Degenerative cervical myelopathy (DCM) is a common condition, which despite treatment, will leave most with disabilities: research progress is urgently needed to improve outcomes.
Research targeted to the priorities of those working and living with a disease is demonstrated to accelerate practice changing research. This is unknown in DCM. The James Lind Alliance (JLA) is an organisation founded to coordinate and quality assure priority setting initiatives. AOSpine RECODE-DCM [Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy] is a JLA priority setting initiative for DCM, led by the AOSpine Spinal Cord Injury Knowledge Forum.

Aims
To identify the top 10 unanswered research questions (‘research priorities’) in DCM.

Methods
AOSpine RECODE-DCM is an international, multi-stakeholder, JLA priority setting initiative. The published protocol is found here (doi: 10.1177/2192568219832855). In short, two iterative online surveys and a face to face consensus meeting were used to establish consensus. Perspective was sought from three key stakeholder groups: spinal surgeons, PwCM and other health care professionals (OHP). The first survey gathered research ideas, using subcategories of diagnosis, management, long-term care and miscellaneous. Ideas were reviewed, and thematically categorised into summary questions. Answered questions identified through evidence checking were excluded. In the second survey, respondents shortlisted their top 10. The top questions were then discussed and ranked at a face-to-face consensus meeting (New York, November 2019) to generate a final list of top 10 priorities. The process was overseen by a multi-stakeholder, international steering committee.

Results
429 participants (59% Surgeons, 21% PwCM and 20% OHP) submitted >3500 research suggestions. 74 unanswered summary questions were shortlisted by 417 participants (56% Surgeons, 26% PwCM and 23% OHP). 26 questions were discussed and ranked at the consensus meeting. The final top-10 included increasing DCM awareness, novel diagnostics, surgical decision making, adjuvant management, understanding mechanisms and developing novel therapies. This list can be found at (https://tinyurl.com/ISCOS-Abstract) and includes:
1) What strategies can increase awareness and understanding of DCM
2) What is the natural history of DCM and what factors affect this?
3) What are the diagnostic criteria of DCM?
4) What assessment tools can be used to evaluate functional impairment, disability and quality of life in people with DCM?
5) What is the pathophysiological mechanism of DCM?
6) What is the role of rehabilitation following surgery for DCM?
7) Can novel therapies, including stem-cell, gene, pharmacological and neuroprotective therapies, improve the health and wellbeing of people living with DCM?
8) What is the socio-economic impact of DCM?
9) What is the role of dynamic or novel imaging techniques and neurophysiology?
10) What are the clinical and imaging factors that can help a surgeon select who should undergo surgical decompression?



Conclusions
AOSpine RECODE-DCM has established the top research priorities for DCM. These objectives should be a focus for the field, to accelerate advances in care that change outcomes. The AOSpine RECODE-DCM project continues with a number of other objectives, to develop a DCM research toolkit that can help researchers changes outcomes sooner. More information at (www.recode-dcm.com).

Object: Multilineage-differentiating stress-enduring (Muse) cells are pluripotent stem cells, which can be harvested from the bone marrow. After transplantation, Muse cells can migrate to an injured site of the body and exert repair effects. However, it remains unknown whether Muse cell transplantation can be an effective treatment in spinal cord injury.
Methods: We used a rat model of thoracic spinal cord contusion injury. For Muse cells transplantation, clinical product “CL2020” containing 300,000 Muse cells were administered intravenously one day after the mid-thoracic injury. Animals were divided into CL2020 (n=11) and the vehicle treated (n=15) groups. Behavioral and histological evaluations were conducted over 8 weeks to see whether intravenous CL2020 administration provide therapeutic effects for spinal cord injury.
Results: Hindlimb motor function significantly improved after CL2020 transplantations. Importantly, the effects were reverted by the human-selective diphtheria toxin. In immunohistochemical analyses, cystic cavity formed after the injury was smaller in CL2020 group. Furthermore, more numbers of descending 5-HT fibers were preserved distal to the injury site after CL2020 administration. Eight weeks after the injury, Muse cells in CL2020 were confirmed to differentiate into neuronal cells in the injured spinal cord.
Conclusions: Acutely after SCI, Muse cells in CL2020 can reach to the injured spinal cord after intravenous administration and differentiate into neuronal cells. Muse cells in CL2020 facilitated nerve fibers preservation, and exert therapeutic potential for severe SCI.

Introduction: In animal models of spinal cord injury, inflammation post-trauma activates neural stem and progenitor cells (NSPCs) which differentiate into glial scar astrocytes. To direct NSPC fate and promote regeneration instead, NSPCs can be targeted using growth factors. However, the mechanisms regulating human spinal cord NSPC pathophysiology and regeneration are not known. Therefore, to improve the translation of animal therapies for spinal cord injury, we assessed the effect of inflammatory and regenerative factors on primary NSPCs in a small (rat) and large (pig) animal model in comparison to NSPCs from humans.
Methods: Primary spinal cord NSPCs from adult humans (n=8), pigs (n=5) and rats (n=6) were cultured using the neurosphere assay. To mimic post-injury inflammation, primary-derived NSPCs were treated with pro-inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), or transforming growth factor-β (TGFβ). To direct regeneration, NSPCs were treated with retinoic acid (RA), platelet-derived growth factor (PDGFα), or bone morphogenic protein-(BMP4) to induce neurons, oligodendrocytes or astrocytes, respectively. Cultures were treated for 7 or 14 days, fixed, and characterized by immunocytochemistry (GFAP, β-iii tubulin, O4, and BrdU). To track proliferation, BrdU was added 24 hours prior to fixation.
Results: IL-6, TNFα, and TGFβ induced astrogenesis of rat NSPCs (3.9±0.7, 5.0±0.9, and 4.0±0.6 fold, respectively) after 7 days concomitant with reduced neurogenesis (0.14±0.90, 0.07±0.04, 0.07±0.05 fold, respectively). Pig NSPCs similarly increased astrogenesis (1.38±0.04, 1.26±0.05, and 1.45±0.04 fold, respectively) but after 14 days of treatment. On the contrary, human NSPCs had reduced astrogenesis (0.14±0.07, 0.6±0.2, and 0.12±0.07 fold, respectively) over the course of 14 days, but generated more neurons (1.23±0.05 and 1.34±0.04 fold, respectively) with IL-6 and TGFβ treatments. With regenerative factor treatment, RA increased neuron differentiation of both human and rat NSPCs, PDGFα increased oligodendrocyte differentiation of only rat NSPCs, and BMP4 increased astrocyte differentiation of human and rat NSPCs at low (40ng/mL) and high (100ng/mL) concentrations, respectively.
Conclusion: For the first time, we have directly compared human, pig, and rat spinal cord NSPC response to pathophysiological and regenerative factors and determined cell-intrinsic differences in behavior. Improved understanding of these differences between human and animal models will be important for the successful translation of regenerative therapies to humans.