Multifaceted Benefits of GDF11 Treatment in Spinal Cord Injury: In Vitro and In Vivo Studies.

Traumatic spinal cord injury (SCI) initiates a series of cellular and molecular events that include both primary and secondary injury cascades. This secondary cascade provides opportunities for the delivery of therapeutic intervention. Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-ß (TGF-ß) superfamily, regulates various biological processes in mammals. The effects of GDF11 in the nervous system were not fully elucidated. Here, we perform extensive in vitro and in vivo studies to unravel the effects of GDF11 on spinal cord after injury. In vitro culture studies showed that GDF11 increased the survival of both neuronal and oligodendroglial cells but decreased microglial cells. In stressed cultures, GDF11 effectively inhibited LPS stimulation and also protected neurons from ischemic damage. Intravenous GDF11 administration to rat after eliciting SCI significantly improved hindlimb functional restoration of SCI rats. Reduced neuronal connectivity was evident at 6 weeks post-injury and these deficits were markedly attenuated by GDF11 treatment. Furthermore, SCI-associated oligodendroglial alteration were more preserved by GDF11 treatment. Taken together, GDF11 infusion via intravenous route to SCI rats is beneficial, facilitating its therapeutic application in the future.

The Application of an Omentum Graft or Flap in Spinal Cord Injury.

BACKGROUND: Spinal cord injury (SCI) causes a primary injury at the lesion site and triggers a secondary injury and prolonged inflammation. There has been no definitive treatment till now. Promoting angiogenesis is one of the most important strategies for functional recovery after SCI. The omentum, abundant in blood and lymph vessels, possesses the potent ability of tissue regeneration. METHODS: The present work examines the efficacy of autologous omentum, either as a flap (with vascular connection intact) or graft (severed vascular connection), on spinal nerve regeneration. After contusive SCI in rats, a thin sheath of omentum was grafted to the injured spinal cord. RESULTS: Omental graft improved behavior scores significantly from the 3rd to 6th week after injury (6th week, 5.5 ± 0.5 vs. 8.6 ± 1.3, p < 0.05). Furthermore, the reduction in cavity and the preservation of class III ß-tubulin-positive nerve fibers in the injury area was noted. Next, the free omental flap was transposed to a completely transected SCI in rats through a pre-implanted tunnel. The flap remained vascularized and survived well several weeks after the operation. At 16 weeks post-treatment, SCI rats with omentum flap treatment displayed the preservation of significantly more nerve fibers (p < 0.05) and a reduced injured cavity, though locomotor scores were similar. CONCLUSIONS: Taken together, the findings of this study indicate that treatment with an omental graft or transposition of an omental flap on an injured spinal cord has a positive effect on nerve protection and tissue preservation in SCI rats. The current data highlight the importance of omentum in clinical applications.

Minimally invasive dynamic screw stabilization using cortical bone trajectory.

BACKGROUND: The conventional pedicle-screw-based dynamic stabilization process involves dissection of the Wiltse plane to cannulate the pedicles, which cannot be undertaken with minimal surgical invasion. Despite some reports having demonstrated satisfactory outcomes of dynamic stabilization in the management of low-grade spondylolisthesis, the extensive soft tissue dissection involved during pedicle screw insertion substantially compromises the designed rationale of motion (muscular) preservation. The authors report on a novel method for minimally invasive insertion of dynamic screws and a mini case series. METHODS: The authors describe innovations for inserting dynamic screws via the cortical bone trajectory (CBT) under spinal navigation. All the detailed surgical procedures and clinical data are demonstrated. RESULTS: A total of four (2 females) patients (mean age 64.75 years) with spinal stenosis at L4-5 were included. By a combination of microscopic decompression and image-guided CBT screw insertion, laminectomy and dynamic screw stabilization were achieved via one small skin incision (less than 3 cm). These patients' back and leg pain improved significantly after the surgery. CONCLUSION: This innovative dynamic screw stabilization via the CBT involved no discectomy (or removal of sequestrated fragment only), no interbody fusion, and little muscle dissection (not even of the Wiltse plane). As a minimally invasive surgery, CBT appeared to be a viable alternative to the conventional pedicle-screw-based dynamic stabilization approach.

Radiological and clinical outcomes of cervical disc arthroplasty for the elderly: a comparison with young patients.

BACKGROUND: This study aimed to investigate whether cervical disc arthroplasty (CDA) would be equally effective in elderly patients as in the young. The inclusion criteria of published clinical trials for CDA-enrolled patients covered the ages from 18 to 78 years. However, there was a paucity of data addressing the differences of outcomes between older and the younger patients. METHODS: A series of consecutive patients who underwent one- or two-level CDA were retrospectively reviewed. Patients at the two extreme ends of the age distribution (≥65 and ≤ 40 years) were selected for comparison. Clinical outcome parameters included visual analog scale (VAS) of neck and arm pain, neck disability index (NDI), and Japanese Orthopaedic Association (JOA) scores. Radiographic outcomes included range of motion (ROM) at the indexed level and evaluation of heterotopic ossification (HO) by computed tomography (CT). Complication profiles were also investigated. RESULTS: There were 24 patients in the elderly group (≥65 years old) and 47 patients in the young group (≤40 years old) with an overall mean follow-up of 28.0 ± 21.97 months. The elderly group had more two-level CDA, and thus the mean operative time was longer (239 vs. 179 min, p < 0.05) than the young group. Both groups had similarly significant improvement in clinical outcomes at the final follow-up. All the replaced disc segments remained mobile on post-operative lateral flexion and extension radiographs. However, the elderly group had a slight decrease in mean ROM (- 0.32° ± 3.93°) at the index level after CDA when compared to that of pre-operation. In contrast, the young group had an increase in mean ROM (+ 0.68° ± 3.60°). The complication profiles were not different, though a trend toward dysphagia was noted in the elderly group (p = 0.073). The incidence or severity (grading) of HO was similar between the two groups. CONCLUSIONS: During the follow-up of two years, CDA was equally effective for patients over 65 years old and those under 40 years in clinical improvement. Although the elderly group demonstrated a small reduction of mean ROM after CDA, in contrast to the young group which had a small increase, the segmental mobility was well preserved at every indexed level for each group.

Characterizing the Neuroprotective Effects of S/B Remedy (Scutellaria baicalensis Georgi and Bupleurum scorzonerifolfium Willd) in Spinal Cord Injury.

The main causes of dysfunction after a spinal cord injury (SCI) include primary and secondary injuries that occur during the first minutes, hours, to days after injury. This treatable secondary cascade provides a window of opportunity for delivering therapeutic interventions. An S/B remedy (Scutellaria baicalensis Georgi and Bupleurum scorzonerifolfium Willd) has anti-inflammatory, cytoprotective, and anticarcinogenic effects in liver or neurodegenerative diseases. The present work examined the effect of S/B on injured spinal cord neurons in cultures and in vivo. S/B effectively reduced peroxide toxicity and lipopolysaccharide stimulation in both spinal cord neuron/glial and microglial cultures with the involvement of PKC and HSP70. The effect of S/B was further conducted in contusive SCI rats. Intraperitoneal injections of S/B to SCI rats preserved spinal cord tissues and effectively attenuated microglial activation. Consistently, S/B treatment significantly improved hindlimb functions of SCI rats. In the acute stage of injury, S/B treatment markedly reduced the levels of ED1 expression and lactate and had a tendency to decrease lipid peroxidation. Taken together, we demonstrated long-term hindlimb restoration alongside histological improvements with systemic S/B remedy treatment in a clinically relevant model of contusive SCI. Our findings highlight the potential of an S/B remedy for acute therapeutic intervention after SCI.

Improving the regenerative potential of olfactory ensheathing cells by overexpressing prostacyclin synthetase and its application in spinal cord repair.

BACKGROUND: Olfactory ensheathing cells (OEC), specialized glia that ensheathe bundles of olfactory nerves, have been reported as a favorable substrate for axonal regeneration. Grafting OEC to injured spinal cord appears to facilitate axonal regeneration although the functional recovery is limited. In an attempt to improve the growth-promoting properties of OEC, we transduced prostacyclin synthase (PGIS) to OEC via adenoviral (Ad) gene transfer and examined the effect of OEC with enhanced prostacyclin synthesis in co-culture and in vivo. Prostacyclin is a vasodilator, platelet anti-aggregatory and cytoprotective agent. RESULTS: Cultured OEC expressed high level of cyclooxygneases, but not PGIS. Infection of AdPGIS to OEC could selectively augument prostacyclin synthesis. When cocultured with either OEC or AdPGIS-OEC, neuronal cells were resistant to OGD-induced damage. The resulted OEC were further transplanted to the transected cavity of thoracic spinal cord injured (SCI) rats. By 6 weeks post-surgery, significant functional recovery in hind limbs occurred in OEC or AdPGIS-OEC transplanted SCI rats compared with nontreated SCI rats. At 10-12 weeks postgraft, AdPGIS-OEC transplanted SCI rats showed significantly better motor restoration than OEC transplanted SCI rats. Futhermore, regenerating fiber tracts in the distal spinal cord stump were found in 40-60% of AdPGIS-OEC transplanted SCI rats. CONCLUSIONS: Enhanced synthesis of prostacyclin in grafted OEC improved fiber tract regeneration and functional restoration in spinal cord injured rats. These results suggest an important potential of prostacyclin in stimulating OEC therapeutic properties that are relevant for neural transplant therapies.

Hybrid cervical disc arthroplasty.

For patients with multilevel cervical stenosis at nonadjacent segments, one of the traditional approaches has included a multilevel fusion of the abnormal segments as well as the intervening normal segment. In this video we demonstrate an alternative treatment plan with tailored use of a combination of anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) with an intervening skipped level. The authors present the case of a 72-year-old woman with myeloradiculopathy and a large disc herniation with facet joint degeneration at C3-4 and bulging disc at C5-6. After nonoperative treatment failed, she underwent a single-level ACDF at C3-4 and single-level arthroplasty at C5-6, which successfully relieved her symptoms. No intervention was performed at the normal intervening C4-5 segment. By using ACDF combined with arthroplasty, the authors have avoided a 3-level fusion for this patient and maintained the range of motion of 2 disc levels. The video can be found here: https://youtu.be/OrxcPUBvqLk .

Resection of uncovertebral joints and posterior longitudinal ligament for cervical disc arthroplasty.

The most commonly accepted indications for cervical disc arthroplasty (CDA) are 1- and 2-level cervical disc herniation or spondylosis causing radiculopathy or myelopathy that is refractory to medical management. Unlike anterior cervical discectomy and fusion (ACDF), which eliminates motion, CDA aims to restore the physiological range of motion of the indexed joint. Thus, the effect of indirect decompression gained by the insertion of a sufficiently large interbody graft and incorporation into arthrodesis after ACDF cannot be duplicated for CDA. For patients undergoing CDA, during extreme flexion/extension or rotation, the exiting nerve roots might be impinged by inadequately decompressed foraminal osteophytes. Therefore, the authors advocate generous decompression, including resection of the posterior longitudinal ligament (PLL) and bilateral uncovertebral joints (UVJs), even in the asymptomatic side. This video demonstrates full dural expansion and enlarged neuroforamen after removal of the PLL and UVJs. Venous hemorrhage encountered during foraminotomy can always be controlled by cottonoid packing or hemostatic agents. Also, the endplates of the surrounding vertebral bodies were meticulously prepared for parallel insertion of the ProDisc-C Nova (DePuy Synthes Spine) artificial disc. Please note that the ProDisc-C Nova is currently not available on the US market. The video can be found here: https://youtu.be/XUo34j6WFYs .

Can segmental mobility be increased by cervical arthroplasty?

OBJECTIVE Many reports have successfully demonstrated that cervical disc arthroplasty (CDA) can preserve range of motion after 1- or 2-level discectomy. However, few studies have addressed the extent of changes in segmental mobility after CDA or their clinical correlations. METHODS Data from consecutive patients who underwent 1-level CDA were retrospectively reviewed. Indications for surgery were medically intractable degenerative disc disease and spondylosis. Clinical outcomes, including visual analog scale (VAS)-measured neck and arm pain, Neck Disability Index (NDI), and Japanese Orthopaedic Association (JOA) scores, were analyzed. Radiographic outcomes, including C2-7 Cobb angle, the difference between pre- and postoperative C2-7 Cobb angle (ΔC2-7 Cobb angle), sagittal vertical axis (SVA), the difference between pre- and postoperative SVA (ΔSVA), segmental range of motion (ROM), and the difference between pre- and postoperative ROM (ΔROM), were assessed for their association with clinical outcomes. All patients underwent CT scanning, by which the presence and severity of heterotopic ossification (HO) were determined during the follow-up. RESULTS A total of 50 patients (mean age 45.6 ± 9.33 years) underwent a 1-level CDA (Prestige LP disc) and were followed up for a mean duration of 27.7 ± 8.76 months. All clinical outcomes, including VAS, NDI, and JOA scores, improved significantly after surgery. Preoperative and postoperative ROM values were similar (mean 9.5° vs 9.0°, p > 0.05) at each indexed level. The mean changes in segmental mobility (ΔROM) were -0.5° ± 6.13°. Patients with increased segmental mobility after surgery (ΔROM > 0°) had a lower incidence of HO and HO that was less severe (p = 0.048) than those whose ΔROM was < 0°. Segmental mobility (ROM) was significantly lower in patients with higher HO grade (p = 0.012), but it did not affect the clinical outcomes. The preoperative and postoperative C2-7 Cobb angles and SVA remained similar. The postoperative C2-7 Cobb angles, SVA, ΔC2-7 Cobb angles, and ΔSVA were not correlated to clinical outcomes after CDA. CONCLUSIONS Segmental mobility (as reflected by the mean ROM) and overall cervical alignment (i.e., mean SVA and C2-7 Cobb angle) had no significant impact on clinical outcomes after 1-level CDA. Patients with increased segmental mobility (ΔROM > 0°) had significantly less HO and similarly improved clinical outcomes than those with decreased segmental mobility (ΔROM < 0°).

Stepwise illustration of teeth-fixation semi-constrained cervical disc arthroplasty.

There are many kinds of artificial discs available for cervical disc arthroplasty (CDA), with various designs of fixation and articulation mechanisms. Each of these designs has different features and theoretically fits most optimally in selected types of patients. However, there has been insufficient literature to guide individualized selection among these CDA devices. Since CDA aims to restore the joint function rather than arthrodesis, tailor-made size, shape, and mechanical properties should be taken into account for each candidate's target disc. Despite several large-scale prospective randomized control trials that have demonstrated the effectiveness and durability of CDA for up to 8 years, none of them involved more than one kind of artificial disc. In this video the authors present detailed steps and technical aspects of the newly introduced ProDisc-C Vivo (DePuy Synthes Spine), which has the same ball-and-socket design for controlled, predictable motion as the ProDisc-C. The newly derived teeth fixation provides high primary stability and multilevel capability by avoidance of previous keel-related limitations and complications (e.g., split vertebral fracture). Please note that the ProDisc-C Vivo is currently not available on the US market. The authors present the case of a 53-year-old woman who had symptoms of both radiculopathy and myelopathy caused by a large, calcified disc herniation at C4-5. There was no improvement after 4 months of medical treatment and rehabilitation. A single-level CDA was successfully performed with the ProDisc-C Vivo, and her symptoms were completely ameliorated afterward. The follow-up images demonstrated preservation of motion at the indexed level. The video can be found here: https://youtu.be/4DSES1xgvQU .

Natural Compounds from Herbs that can Potentially Execute as Autophagy Inducers for Cancer Therapy.

Accumulated evidence indicates that autophagy is a response of cancer cells to various anti-cancer therapies. Autophagy is designated as programmed cell death type II, and is characterized by the formation of autophagic vacuoles in the cytoplasm. Numerous herbs, including Chinese herbs, have been applied to cancer treatments as complementary and alternative medicines, supplements, or nutraceuticals to dampen the side or adverse effects of chemotherapy drugs. Moreover, the tumor suppressive actions of herbs and natural products induced autophagy that may lead to cell senescence, increase apoptosis-independent cell death or complement apoptotic processes. Hereby, the underlying mechanisms of natural autophagy inducers are cautiously reviewed in this article. Additionally, three natural compounds-curcumin, 16-hydroxycleroda-3,13-dien-15,16-olide, and prodigiosin-are presented as candidates for autophagy inducers that can trigger cell death in a supplement or alternative medicine for cancer therapy. Despite recent advancements in therapeutic drugs or agents of natural products in several cancers, it warrants further investigation in preclinical and clinical studies.

The immunomodulator decoy receptor 3 improves locomotor functional recovery after spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) causes loss of neurons and axons and results in motor and sensory function impairments. SCI elicits an inflammatory response and induces the infiltration of immune cells, predominantly macrophages, to the injured site. Decoy receptor 3 (DcR3), also known as tumor necrosis factor receptor superfamily member (TNFRSF)-6B, is a pleiotropic immunomodulator capable of inducing macrophage differentiation into the M2 phenotype and enhancing angiogenesis. Because M2 macrophages are crucial for the recovery of impaired motor functions, we ask whether DcR3 is beneficial for the functional recovery of locomotion in Sprague-Dawley (SD) rats after SCI. METHODS: Contusion injury of the spinal cord was performed using a New York University impactor at the ninth thoracic vertebrae, followed by intrathecal injection of 15 µg recombinant protein comprising DcR3 (DcR3.Fc) in 5 µl of normal saline as the treatment, or 5 µl of normal saline as the control, into the injury epicenter. Functional recovery was evaluated using an open-field test weekly up to 6 weeks after injury. The cavity size and myelin sparing in the rostral-to-caudal region, including the epicenter of the injury, were then examined in SCI rats by histological staining. The expression of anti-inflammatory cytokines and the presence of M2 macrophages were determined by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry at 7 day after SCI. Statistical analysis was performed using a two-tailed Student's t test. RESULTS: Intrathecal administration of DcR3.Fc significantly improved locomotor function and reduced secondary injury with a smaller wound cavity and increased myelin sparing at the lesion site. Compared with the control group, DcR3.Fc-treated rats had increased vascularization at the injury epicenter along with higher levels of interleukin (IL)-4 and IL-10 and lower level of IL-1ß on DcR3.Fc-treated rats at day 7 after SCI. Moreover, higher levels of arginase I (Arg I) and CD206 (M2 macrophage markers) and RECA-1 (endothelial marker) were observed in the epicenter on day 7 after SCI by immunofluorescence staining. CONCLUSIONS: These results indicated that DcR3.Fc may promote the M2 macrophage infiltration and enhanced angiogenesis at the lesion site, thus preserving a greater amount of spinal cord tissues and enhancing functional recovery after SCI.

Risk of spinal cord injury in patients with cervical spondylotic myelopathy and ossification of posterior longitudinal ligament: a national cohort study.

OBJECTIVE This study aimed to estimate the risk of spinal cord injury (SCI) in patients with cervical spondylotic myelopathy (CSM) with and without ossification of posterior longitudinal ligament (OPLL). Also, the study compared the incidence rates of SCI in patients who were managed surgically and conservatively. METHODS This retrospective cohort study covering 15 years analyzed the incidence of SCI in patients with CSM. All patients, identified from the National Health Insurance Research Database, were hospitalized with the diagnosis of CSM and followed up during the study period. These patients with CSM were categorized into 4 groups according to whether they had OPLL or not and whether they received surgery or not: 1) surgically managed CSM without OPLL; 2) conservatively managed CSM without OPLL; 3) surgically managed CSM with OPLL; and 4) conservatively managed CSM with OPLL. The incidence rates of subsequent SCI in each group during follow-up were then compared. Kaplan-Meier and Cox regression analyses were performed to compare the risk of SCI between the groups. RESULTS Between January 1, 1999, and December 31, 2013, there were 17,258 patients with CSM who were followed up for 89,003.78 person-years. The overall incidence of SCI in these patients with CSM was 2.022 per 1000 person-years. Patients who had CSM with OPLL and were conservatively managed had the highest incidence of SCI, at 4.11 per 1000 person-years. Patients who had CSM with OPLL and were surgically managed had a lower incidence of SCI, at 3.69 per 1000 person-years. Patients who had CSM without OPLL and were conservatively managed had an even lower incidence of SCI, at 2.41 per 1000 person-years. Patients who had CSM without OPLL and were surgically managed had the lowest incidence of SCI, at 1.31 per 1000 person-years. The Cox regression model demonstrated that SCIs are significantly more likely to happen in male patients and in those with OPLL (HR 2.00 and 2.24, p < 0.001 and p = 0.007, respectively). Surgery could significantly lower the risk for approximately 50% of patients (HR 0.52, p < 0.001). CONCLUSIONS Patients with CSM had an overall incidence rate of SCI at approximately 0.2% per year. Male sex, the coexistence of OPLL, and conservative management are twice as likely to be associated with subsequent SCI. Surgery is therefore suggested for male patients with CSM who also have OPLL.

Dynamic stabilization for L4-5 spondylolisthesis: comparison with minimally invasive transforaminal lumbar interbody fusion with more than 2 years of follow-up.

OBJECTIVE In the past decade, dynamic stabilization has been an emerging option of surgical treatment for lumbar spondylosis. However, the application of this dynamic construct for mild spondylolisthesis and its clinical outcomes remain uncertain. This study aimed to compare the outcomes of Dynesys dynamic stabilization (DDS) with minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) for the management of single-level spondylolisthesis at L4-5. METHODS This study retrospectively reviewed 91 consecutive patients with Meyerding Grade I spondylolisthesis at L4-5 who were managed with surgery. Patients were divided into 2 groups: DDS and MI-TLIF. The DDS group was composed of patients who underwent standard laminectomy and the DDS system. The MI-TLIF group was composed of patients who underwent MI-TLIF. Clinical outcomes were evaluated by visual analog scale for back and leg pain, Oswestry Disability Index, and Japanese Orthopaedic Association scores at each time point of evaluation. Evaluations included radiographs and CT scans for every patient for 2 years after surgery. RESULTS A total of 86 patients with L4-5 spondylolisthesis completed the follow-up of more than 2 years and were included in the analysis (follow-up rate of 94.5%). There were 64 patients in the DDS group and 22 patients in the MI-TLIF group, and the overall mean follow-up was 32.7 months. Between the 2 groups, there were no differences in demographic data (e.g., age, sex, and body mass index) or preoperative clinical evaluations (e.g., visual analog scale back and leg pain, Oswestry Disability Index, and Japanese Orthopaedic Association scores). The mean estimated blood loss of the MI-TLIF group was lower, whereas the operation time was longer compared with the DDS group (both p < 0.001). For both groups, clinical outcomes were significantly improved at 6, 12, 18, and 24 months after surgery compared with preoperative clinical status. Moreover, there were no differences between the 2 groups in clinical outcomes at each evaluation time point. Radiological evaluations were also similar and the complication rates were equally low in both groups. CONCLUSIONS At 32.7 months postoperation, the clinical and radiological outcomes of DDS were similar to those of MI-TLIF for Grade I degenerative spondylolisthesis at L4-5. DDS might be an alternative to standard arthrodesis in mild lumbar spondylolisthesis. However, unlike fusion, dynamic implants have issues of wearing and loosening in the long term. Thus, the comparable results between the 2 groups in this study require longer follow-up to corroborate.

Dynesys dynamic stabilization-related facet arthrodesis.

OBJECTIVE Dynamic stabilization devices are designed to stabilize the spine while preserving some motion. However, there have been reports demonstrating limited motion at the instrumented level of the lumbar spine after Dynesys dynamic stabilization (DDS). The causes of this limited motion and its actual effects on outcomes after DDS remain elusive. In this study, the authors investigate the incidence of unintended facet arthrodesis after DDS and clinical outcomes. METHODS This retrospective study included 80 consecutive patients with 1- or 2-level lumbar spinal stenosis who underwent laminectomy and DDS. All medical records, radiological data, and clinical evaluations were analyzed. Imaging studies included pre- and postoperative radiographs, MR images, and CT scans. Clinical outcomes were measured by a visual analog scale (VAS) for back and leg pain, the Oswestry Disability Index (ODI), and Japanese Orthopaedic Association (JOA) scores. Furthermore, all patients had undergone postoperative CT for the detection of unintended arthrodesis of the facets at the indexed level, and range of motion was measured on standing dynamic radiographs. RESULTS A total of 70 patients (87.5%) with a mean age of 64.0 years completed the minimum 24-month postoperative follow-up (mean duration 29.9 months). Unintended facet arthrodesis at the DDS instrumented level was demonstrated by CT in 38 (54.3%) of the 70 patients. The mean age of patients who had facet arthrodesis was 9.8 years greater than that of the patients who did not (68.3 vs 58.5 years, p = 0.009). There were no significant differences in clinical outcomes, including VAS back and leg pain, ODI, and JOA scores between patients with and without the unintended facet arthrodesis. Furthermore, those patients older than 60 years were more likely to have unintended facet arthrodesis (OR 12.42) and immobile spinal segments (OR 2.96) after DDS. Regardless of whether unintended facet arthrodesis was present or not, clinical evaluations demonstrated improvement in all patients (all p < 0.05). CONCLUSIONS During the follow-up of more than 2 years, unintended facet arthrodesis was demonstrated in 54.3% of the patients who underwent 1- or 2-level DDS. Older patients (age > 60 years) were more likely to have unintended facet arthrodesis and subsequent immobile spinal segments. However, unintended facet arthrodesis did not affect the clinical outcomes during the study period. Further evaluations are needed to clarify the actual significance of this phenomenon.

Cervical Arthroplasty for Traumatic Disc Herniation: An Age- and Sex-matched Comparison with Anterior Cervical Discectomy and Fusion.

BACKGROUND: The efficacy and safety of using cervical arthroplasty for degenerative disc disease have been demonstrated by prospective, randomized and controlled clinical trials. However, there are scant data on using cervical arthroplasty for traumatic disc herniation. Therefore, this study aimed to investigate the outcomes of patients who underwent cervical arthroplasty for traumatic disc herniation. METHODS: This cohort included patients who were admitted through the emergency department for trauma. Only patients who had newly-onset, one- or two-level cervical disc disease causing radiculopathy or myelopathy were identified. None of these patients had previously sought for medical attention for such problems. Those patients who had severe spinal cord injury (i.e. American Spinal Injury Association scale A, B or C) or severe myelopathy (i.e. Nurick scale 4 or 5), bony fracture, dislocation, perched facet, kyphotic deformity, or instability were also excluded. An age- and sex-matched one-to-one comparison was made between patients who underwent cervical arthroplasty, on the one hand, and anterior cervical discectomy and fusion (ACDF). RESULTS: A total of 30 trauma patients (15 in the arthroplasty group and 15 in the ACDF group) were analyzed, with a mean follow-up of 29.6 months. The demographic data were similar. Post-operation, the arthroplasty group had significant improvement in VAS of neck and arm pain, JOA, and NDI when compared to their pre-operation status. Similarly, the ACDF group also improved significantly after the operation. There were no differences between the two groups in post-operative VAS neck and arm pain, and JOA scores. The arthroplasty group maintained a range of motion in the indexed levels and had better NDI scores at 6-months post-operation than the ACDF group. CONCLUSIONS: For selected patients (i.e. no spinal cord injury, no fracture, and no instability) with traumatic cervical disc herniation, cervical arthroplasty yields similar improvement in clinical outcomes to ACDF and preserves segmental mobility.

The influence of shoulder pain on functional limitation, perceived health, and depressive mood in patients with traumatic paraplegia.

OBJECTIVE: To assess whether functional activity, perceived health, and depressive symptoms differ between individuals with traumatic paraplegia with and without shoulder pain. DESIGN: Cross sectional and comparative investigation using the unified questionnaire. SETTING: Neural Regeneration and Repair Division unit of Taipei Veterans General Hospital in Taiwan. PARTICIPANTS: Seventy-six patients with paraplegia (23 with and 53 without shoulder pain) who had experienced spinal cord injury at American Spinal Injury Association Impairment Scale T2 to T12 neurologic level (at least 6 months previously). OUTCOME MEASURES: Spinal Cord Independence Measure (SCIM), a single item from the Medical Outcomes Study 36-Item Short-Form Health Survey, and Patient Health Questionnaire-9 (PHQ-9) depression scale. RESULTS: Shoulder pain was prevalent in 30% patients. Patients with shoulder pain had significantly worse perceived health and greater depressive symptoms than those without. No significant difference was found in functional ability between groups. Greater shoulder pain intensity was related to higher depressive scores (r=0.278, P=0.017) and lower self-perceived health scores (r=-0.433, P<0.001) but not SCIM scores (P=0.342). CONCLUSION: Although shoulder pain was unrelated to functional limitation, it was associated with lower perceived health and higher depressive mood levels.

Cytoprotective and anti-inflammatory effects of PAL31 overexpression in glial cells.

BACKGROUND: Acute spinal cord injury (SCI) leads to a series of reactive changes and causes severe neurological deficits. A pronounced inflammation contributes to secondary pathology after SCI. Astroglia respond to SCI by proliferating, migrating, and altering phenotype. The impact of reactive gliosis on the pathogenesis of SCI is not fully understood. Our previous study has identified an inflammatory modulating protein, proliferation related acidic leucine-rich protein (PAL31) which is upregulated in the microglia/macrophage of injured cords. Because PAL31 participates in cell cycle progression and reactive astroglia often appears in the injured cord, we aim to examine whether PAL31 is involved in glial modulation after injury. RESULTS: Enhanced PAL31 expression was shown not only in microglia/macrophages but also in spinal astroglia after SCI. Cell culture study reveal that overexpression of PAL31 in mixed glial cells or in C6 astroglia significantly reduced LPS/IFNγ stimulation. Further, enhanced PAL31 expression in C6 astroglia protected cells from H2O2 toxicity; however, this did not affect its proliferative activity. The inhibiting effect of PAL31 on LPS/IFNγ stimulation was observed in glia or C6 after co-culture with neuronal cells. The results demonstrated that the overexpressed PAL31 in glial cells protected neuronal damages through inhibiting NF-kB signaling and iNOS. CONCLUSIONS: Our data suggest that PAL31upregulation might be beneficial after spinal cord injury. Reactive gliosis might become a good target for future therapeutic interventions.

Recovery of neurological function of ischemic stroke by application of conditioned medium of bone marrow mesenchymal stem cells derived from normal and cerebral ischemia rats.

BACKGROUND: Several lines of evidence have demonstrated that bone marrow-derived mesenchymal stem cells (BM-MSC) release bioactive factors and provide neuroprotection for CNS injury. However, it remains elusive whether BM-MSC derived from healthy donors or stroke patients provides equal therapeutic potential. The present work aims to characterize BM-MSC prepared from normal healthy rats (NormBM-MSC) and cerebral ischemia rats (IschBM-MSC), and examine the effects of their conditioned medium (Cm) on ischemic stroke animal model. RESULTS: Isolated NormBM-MSC or IschBM-MSC formed fibroblastic like morphology and expressed CD29, CD90 and CD44 but failed to express the hematopoietic marker CD34. The number of colony formation of BM-MSC was more abundant in IschBM-MSC than in NormBM-MSC. This is in contrast to the amount of Ficoll-fractionated mononuclear cells from normal donor and ischemic rats. The effect of cm of BM-MSC was further examined in cultures and in middle cerebral artery occlusion (MCAo) animal model. Both NormBM-MSC Cm and IschBM-MSC Cm effectively increased neuronal connection and survival in mixed neuron-glial cultures. In vivo, intravenous infusion of NormBM-MSC Cm and IschBM-MSC Cm after stroke onset remarkably improved functional recovery. Furthermore, NormBM-MSC Cm and IschBM-MSC Cm increased neurogenesis and attenuated microglia/ macrophage infiltration in MCAo rat brains. CONCLUSIONS: Our data suggest equal effectiveness of BM-MSC Cm derived from ischemic animals or from a normal population. Our results thus revealed the potential of BM-MSC Cm on treatment of ischemic stroke.

Differences between arthroplasty and anterior cervical fusion in two-level cervical degenerative disc disease.

PURPOSE: Although arthroplasty is an accepted option for two-level disease, there is a paucity of data regarding outcomes of two-level cervical arthroplasty. The current study was designed to determine differences between two-level cervical arthroplasty and anterior fusion. METHODS: Seventy-seven consecutive patients who underwent two-level anterior cervical operations for degenerative disc disease were divided into the arthroplasty (37 patients) and fusion (40 patients) groups. Clinical outcomes were measured by Visual Analogue Scale (VAS) of neck and arm pain, Japanese Orthopedic Association (JOA) scores, and Neck Disability Index (NDI). Every patient was evaluated by radiography and computed tomography for fusion or detection of heterotopic ossification. RESULTS: Thirty-seven patients (with 74 levels of Bryan discs) were compared with 40 patients who had two-level anterior fusion (mean follow-up of 39.6 ± 6.7 months). There was no difference in sex, but the mean age of the arthroplasty group was significantly younger (52.1 ± 9.1 vs. 63.0 ± 10.6 years, p < 0.001). The mean estimated blood loss was similar (p = 0.135), but the mean operation time was longer in the arthroplasty group (315.5 ± 82.0 versus 224.9 ± 61.8 min, p < 0.001). At 24 months post-operation, the arthroplasty group had increased their range of motion than pre-operation (23.5° versus 20.1°, p = 0.018). There were significant improvements in neck or arm VAS, JOA scores, and NDI in both groups. However, there were no differences in clinical outcomes or adverse events between the two groups. CONCLUSIONS: Clinical outcomes of two-level arthroplasty and anterior cervical fusion are similar 39.6 months after surgery. Cervical arthroplasty preserves mobility at the index levels without increased adverse effects.