Unraveling quad fever: Severe hyperthermia after traumatic cervical spinal cord injury.

PURPOSE: There are many infectious and inflammatory causes for elevated core-body temperatures, though they rarely pass 40 â„ƒ (104 ℉). The term "quad fever" is used for extreme hyperpyrexia in the setting of acute cervical spinal cord injuries (SCIs). The traditional methods of treating hyperpyrexia are often ineffective and reported morbidity and mortality rates approach 100%. This study aims to identify the incidence of elevated temperatures in SCIs at our institution and assess the effectiveness of using a non-invasive dry water temperature management system as a treatment modality with mortality. METHODS: A retrospective analysis of acute SCI patients requiring surgical intensive care unit admission who experienced fevers ≥ 40 â„ƒ (104 ℉) were compared to patients with maximum temperatures < 40 â„ƒ. Patients ≥18 years old who sustained an acute traumatic SCI were included in this study. Patients who expired in the emergency department; had a SCI without radiologic abnormality; had neuropraxia; were admitted to any location other than the surgical intensive care unit; or had positive blood cultures were excluded. SAS 9.4 was used to conduct statistical analysis. RESULTS: Over the 9-year study period, 35 patients were admitted to the surgical intensive care unit with a verified SCI. Seven patients experienced maximum temperatures of ≥ 40 â„ƒ. Six of those patients were treated with the dry water temperature management system with an overall mortality of 57.1% in this subgroup. The mortality rate for the 28 patients who experienced a maximum temperature of ≤ 40 â„ƒ was 21.4% (p = 0.16). CONCLUSION: The diagnosis of quad fever should be considered in patients with cervical SCI in the presence of hyperthermia. In this study, there was no significant difference in mortality between quad fever patients treated with a dry water temperature management system versus SCI patients without quad fever. The early use of a dry water temperature management system appears to decrease the mortality rate of quad fever.

Unraveling quad fever: Severe hyperthermia after traumatic cervical spinal cord injury / 中华创伤杂志(英文版)

PURPOSE@#There are many infectious and inflammatory causes for elevated core-body temperatures, though they rarely pass 40 ℃ (104 ℉). The term "quad fever" is used for extreme hyperpyrexia in the setting of acute cervical spinal cord injuries (SCIs). The traditional methods of treating hyperpyrexia are often ineffective and reported morbidity and mortality rates approach 100%. This study aims to identify the incidence of elevated temperatures in SCIs at our institution and assess the effectiveness of using a non-invasive dry water temperature management system as a treatment modality with mortality.@*METHODS@#A retrospective analysis of acute SCI patients requiring surgical intensive care unit admission who experienced fevers ≥ 40 ℃ (104 ℉) were compared to patients with maximum temperatures < 40 ℃. Patients ≥18 years old who sustained an acute traumatic SCI were included in this study. Patients who expired in the emergency department; had a SCI without radiologic abnormality; had neuropraxia; were admitted to any location other than the surgical intensive care unit; or had positive blood cultures were excluded. SAS 9.4 was used to conduct statistical analysis.@*RESULTS@#Over the 9-year study period, 35 patients were admitted to the surgical intensive care unit with a verified SCI. Seven patients experienced maximum temperatures of ≥ 40 ℃. Six of those patients were treated with the dry water temperature management system with an overall mortality of 57.1% in this subgroup. The mortality rate for the 28 patients who experienced a maximum temperature of ≤ 40 ℃ was 21.4% (p = 0.16).@*CONCLUSION@#The diagnosis of quad fever should be considered in patients with cervical SCI in the presence of hyperthermia. In this study, there was no significant difference in mortality between quad fever patients treated with a dry water temperature management system versus SCI patients without quad fever. The early use of a dry water temperature management system appears to decrease the mortality rate of quad fever.

A man with severed spine is able to walk again following implantation of electrical stimulation device.

Patients with devastating spinal cord injuries regained the ability to stand, walk, and perform even more complex motor functions after receiving implants that deliver epidural electrical stimulation.

Prospective analysis of a surgical algorithm to achieve ventilator weaning in cervical tetraplegia.

Objectives: Chronic ventilator dependency in cervical tetraplegia is associated with substantial morbidity. When non-invasive weaning methods have failed the primary surgical treatment is diaphragm pacing. Phrenic nerve integrity and diaphragm motor units are requirements for effective pacing but may need to be restored for successful weaning. A surgical algorithm that includes: 1. Diaphragm pacing, 2. Phrenic nerve reconstruction, and 3. Diaphragm muscle replacement, may provide the capability of reducing or reversing ventilator dependency in virtually all cervical tetraplegics.Design: Prospective case series.Setting: A university-based hospital from 2015 to 2019.Participants: Ten patients with ventilator-dependent cervical tetraplegia.Interventions: I. Pacemaker alone, II. Pacemaker + phrenic nerve reconstruction, or III. Pacemaker + diaphragm muscle replacement.Outcome measures: Time from surgery to observed reduction in ventilator requirements (↓VR), ventilatory needs as of most recent follow-up [no change (NC), partial weaning (PW, 1-12 h/day), or complete weaning (CW, >12 h/day)], and complications.Results: Both patients in Group I achieved CW at 6-month follow-up. Two patients in Group II achieved CW, and in another two patients PW was achieved, at 1.5-2-year follow-up. The remaining two patients are NC at 6 and 8-month follow-up, respectively. In group III, both patients achieved PW at 2-year follow-up. Complications included mucous plugging (n = 1) and pacemaker malfunction requiring revision (n = 3).Conclusion: Although more investigation is necessary, phrenic nerve reconstruction or diaphragm muscle replacement performed (when indicated) with pacemaker implantation may allow virtually all ventilator-dependent cervical tetraplegics to partially or completely wean.

Diaphragm Pacing in Patients with Spinal Cord Injury: A European Experience.

BACKGROUND: Patients with high spinal cord injury (SCI) are unable to breathe on their own and require mechanical ventilation (MV). The long-term use of MV is associated with increased morbidity and mortality. In patients with intact phrenic nerve function, patients can be partially or completely removed from MV by directly stimulating the diaphragm motor points with a diaphragm pacing system (DPS). OBJECTIVES: We describe our multicenter European experience using DPS in SCI patients who required MV. METHODS: We conducted a retrospective study of patients who were evaluated for the implantation of DPS. Patients evaluated for DPS who met the prospectively defined criteria of being at least 1 year of age, and having cervical injury resulting in a complete or partial dependency on MV were included. Patients who received DPS implants were followed for up to 1 year for device usage and safety. RESULTS: Across 3 centers, 47 patients with high SCI were evaluated for DPS, and 34 were implanted. Twenty-one patients had 12 months of follow-up data with a median DPS use of 15 h/day (interquartile range 4, 24). Eight patients (38.1%) achieved complete MV weaning using DPS 24 h/day. Two DPS-related complications were surgical device revision and a wire eruption. No other major complications were associated with DPS use. CONCLUSIONS: Diaphragm pacing represents an attractive alternative stand-alone treatment or adjunctive therapy compared to MV in patients with high SCI. After a period of acclimation, the patients were able to reduce the daily use of MV, and many could be completely removed from MV.

Thoracoscopic intercostal to phrenic nerve transfer for diaphragmatic reanimation in a child with tetraplegia.

Context: To describe for the first time a novel technique of thoracoscopic intercostal nerve mobilization and intercostal to phrenic nerve transfer in the setting of tetraplegia with the goal of reanimating the diaphragm and decreasing ventilator dependence.Findings: A 5-year-old female on 24 h ventilator support secondary to traumatic tetraplegia was evaluated for possible phrenic nerve pacing. Left-sided phrenic nerve stimulation did not result in diaphragmatic contraction indicating a lower motor neuron injury. The patient underwent thoracoscopic mobilization of the left phrenic nerve and 10th intercostal nerve while positioned in the left lateral decubitus position using four 5 mm trocars. The mobilized intercostal nerve was transected close to its distal anterior termination and coapted without tension to the cut end of the terminal phrenic nerve using fibrin sealant. Lastly, phrenic nerve pacer leads and battery were implanted in the chest wall and connected to the electrode placed on the intercostal nerve. One year following the procedure, the patient was tolerating phrenic pacing during the day while requiring ventilation overnight. Currently, the patient is 2 years post-operative from this procedure and does not require ventilator support.Conclusion/clinical relevance: We have shown for the first time a novel approach of thoracoscopic nerve mobilization and phrenic to intercostal nerve transposition to be both safe and effective for restoring innervation of the diaphragm in a child. This minimally invasive procedure is recommended as the preferred approach to reanimate the diaphragm.

Recovery of motor function after traumatic spinal cord injury by using plasma-synthesized polypyrrole/iodine application in combination with a mixed rehabilitation scheme.

Traumatic spinal cord injury (TSCI) can cause paralysis and permanent disability. Rehabilitation (RB) is currently the only accepted treatment, although its beneficial effect is limited. The development of biomaterials has provided therapeutic possibilities for TSCI, where our research group previously showed that the plasma-synthesized polypyrrole/iodine (PPy/I), a biopolymer with different physicochemical characteristics than those of the PPy synthesized by conventional methods, promotes recovery of motor function after TSCI. The present study evaluated if the plasma-synthesized PPy/I applied in combination with RB could increase its beneficial effects and the mechanisms involved. Adult rats with TSCI were divided into no treatment (control); biopolymer (PPy/I); mixed RB by swimming and enriched environment (SW/EE); and combined treatment (PPy/I + SW/EE) groups. Eight weeks after TSCI, the general health of the animals that received any of the treatments was better than the control animals. Functional recovery evaluated by two scales was better and was achieved in less time with the PPy/I + SW/EE combination. All treatments significantly increased ßIII-tubulin (nerve plasticity) expression, but only PPy/I increased GAP-43 (nerve regeneration) and MBP (myelination) expression when were analyzed by immunohistochemistry. The expression of GFAP (glial scar) decreased in treated groups when determined by histochemistry, while morphometric analysis showed that tissue was better preserved when PPy/I and PPy/I + SW/EE were administered. The application of PPy/I + SW/EE, promotes the preservation of nervous tissue, and the expression of molecules related to plasticity as ßIII-tubulin, reduces the glial scar, improves general health and allows the recovery of motor function after TSCI. The implant of the biomaterial polypyrrole/iodine (PPy/I) synthesized by plasma (an unconventional synthesis method), in combination with a mixed rehabilitation scheme with swimming and enriched environment applied after a traumatic spinal cord injury, promotes expression of GAP-43 and ßIII-tubulin (molecules related to plasticity and nerve regeneration) and reduces the expression of GFAP (molecule related to the formation of the glial scar). Both effects together allow the formation of nerve fibers, the reconnection of the spinal cord in the area of injury and the recovery of lost motor function. The figure shows the colocalization (yellow) of ßIII-tubilin (red) and GAP-43 (green) in fibers crossing the epicenter of the injury (arrowheads) that reconnect the rostral and caudal ends of the injured spinal cord and allowed recovery of motor function.

Implantation of Sacral Nerve Stimulator Without Rhizotomy for Neurogenic Bladder in Patient With Spinal Cord Injury: 2-Dimensional Operative Video.

There are approximately 12 000 new individuals with spinal cord injury (SCI) each year, and close to 200 000 individuals live with a SCI-related disability in the United States. The majority of patients with SCI have bladder dysfunction as a result of their injury, with over 75% unable to void volitionally following their injury. In patients with traumatic SCI, intermittent catheterization is commonly recommended, but a lack of adherence to clean intermittent catheterization (CIC) has been observed, with up to 50% discontinuing CIC within 5 yr of injury. The Finetech Brindley Bladder System (FBBS) is an implantable sacral nerve stimulator for improving bladder function in patients with SCI, avoiding the need for CIC. The FDA-approved implantation (Humanitarian Device Exemption H980008) of the FBBS is combined with a posterior rhizotomy to reduce reflex contraction of the bladder, improving continence. However, the posterior rhizotomy is irreversible and has unwanted effects; therefore, the current FDA-approved implantation is being studied without rhizotomy as part of a clinical trial (Investigational Device Exemption G150201) (ClinicalTrials.gov Identifier: NCT02978638). In this video, we present a case of a 66-yr-old female who presented 40-yr status post-T12 SCI, resulting in complete paraplegia and neurogenic bladder not satisfactorily controlled with CIC. We demonstrate the operative steps to complete the implantation of the device without rhizotomy in the first patient enrolled as part of the clinical trial Electrical Stimulation for Continence After SCI (NCT02978638). Appropriate IRB and patient consent were obtained.

Targeted neurotechnology restores walking in humans with spinal cord injury.

Spinal cord injury leads to severe locomotor deficits or even complete leg paralysis. Here we introduce targeted spinal cord stimulation neurotechnologies that enabled voluntary control of walking in individuals who had sustained a spinal cord injury more than four years ago and presented with permanent motor deficits or complete paralysis despite extensive rehabilitation. Using an implanted pulse generator with real-time triggering capabilities, we delivered trains of spatially selective stimulation to the lumbosacral spinal cord with timing that coincided with the intended movement. Within one week, this spatiotemporal stimulation had re-established adaptive control of paralysed muscles during overground walking. Locomotor performance improved during rehabilitation. After a few months, participants regained voluntary control over previously paralysed muscles without stimulation and could walk or cycle in ecological settings during spatiotemporal stimulation. These results establish a technological framework for improving neurological recovery and supporting the activities of daily living after spinal cord injury.

Restoration of motor function after operative reconstruction of the acutely transected spinal cord in the canine model.

BACKGROUND: Cephalosomatic anastomosis or what has been called a "head transplantation" requires full reconnection of the respective transected ends of the spinal cords. The GEMINI spinal cord fusion protocol has been developed for this reason. Here, we report the first randomized, controlled study of the GEMINI protocol in large animals. METHODS: We conducted a randomized, controlled study of a complete transection of the spinal cord at the level of T10 in dogs at Harbin Medical University, Harbin, China. These dogs were followed for up to 8 weeks postoperatively by assessments of recovery of motor function, somato-sensory evoked potentials, and diffusion tensor imaging using magnetic resonance imaging. RESULTS: A total of 12 dogs were subjected to operative exposure of the dorsal aspect of the spinal cord after laminectomy and longitudinal durotomy followed by a very sharp, controlled, full-thickness, complete transection of the spinal cord at T10. The fusogen, polyethylene glycol, was applied topically to the site of the spinal cord transection in 7 of 12 dogs; 0.9% NaCl saline was applied to the site of transection in the remaining 5 control dogs. Dogs were selected randomly to receive polyethylene glycol or saline. All polyethylene glycol-treated dogs reacquired a substantial amount of motor function versus none in controls over these first 2 months as assessed on the 20-point (0-19), canine, Basso-Beattie-Bresnahan rating scale (P<.006). Somatosensory evoked potentials confirmed restoration of electrical conduction cranially across the site of spinal cord transection which improved over time. Diffusion tensor imaging, a magnetic resonance permutation that assesses the integrity of nerve fibers and cells, showed restitution of the transected spinal cord with polyethylene glycol treatment (at-injury level difference: P<.02). CONCLUSION: A sharply and fully transected spinal cord at the level of T10 can be reconstructed with restoration of many aspects of electrical continuity in large animals following the GEMINI spinal cord fusion protocol, with objective evidence of motor recovery and of electrical continuity across the site of transection, opening the way to the first cephalosomatic anastomosis. (Surgery 2017;160:XXX-XXX.).

Increased vascularization promotes functional recovery in the transected spinal cord rats by implanted vascular endothelial growth factor-targeting collagen scaffold.

Spinal cord injury (SCI) is global health concern. The effective strategies for SCI are relevant to the improvement on nerve regeneration microenvironment. Vascular endothelial growth factor (VEGF) is an important cytokine for inducing angiogenesis and accelerating nerve system function recovery from injury. We proposed that VEGF could improve nerve regeneration in SCI. However, an uncontrolled delivery system target to injury site not only decreases the therapeutic efficacy but also increases the risk of tumor information. We implanted collagen scaffold (CS) targeted with a constructed protein, collagen-binding VEGF (CBD-VEGF), to bridge transected spine cord gap in a rat transected SCI model. Functional and histological examinations were conducted to assess the repair capacity of the delivery system CS/CBD-VEGF. The results indicated that the implantation of CS/CBD-VEGF into the model rats improved the survival rate and exerted beneficial effect on functional recovery. The controlled intervention improved the microenvironment, guided axon growth, and promoted neovascularization at the injury site. Therefore, the delivery system with stable binding of VEGF potentially provides a better therapeutic option for SCI. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1024-1034, 2018.

Assessment of Neuroprotective Properties of Melissa officinalis in Combination With Human Umbilical Cord Blood Stem Cells After Spinal Cord Injury.

INTRODUCTION: The pathophysiology of spinal cord injury (SCI) has a classically bad prognosis. It has been demonstrated that human umbilical cord blood stem cells (hUCBSCs) and Melissa officinalis (MO) are useful for the prevention of neurological disease. METHODS: Thirty-six adult male rats were randomly divided into intact, sham, control (SCI), MO, hUCBSC, and MO-hUCBSC groups. Intraperitoneal injection of MO (150 mg/kg) was commenced 24 hr post-SCI and continued once a day for 14 days. Intraspinal grafting of hUCBSCs was commenced immediately in the next day. The motor and sensory functions of all animals were evaluated once a week after the commencement of SCI. Electromyography (EMG) was performed in the last day in order to measure the recruitment index. Immunohistochemistry, reverse transcription-polymerase chain reaction, and transmission electron microscopy evaluations were performed to determine the level of astrogliosis and myelination. RESULTS: The results revealed that motor function (MO-hUCBSC: 15 ± 0.3, SCI: 8.2 ± 0.37, p < .001), sensory function (MO-hUCBSC: 3.57 ± 0.19, SCI: 6.38 ± 0.23, p < .001), and EMG recruitment index (MO-hUCBSC: 3.71 ± 0.18, SCI: 1.6 ± 0.1, p < .001) were significantly improved in the MO-hUCBSC group compared with SCI group. Mean cavity area (MO-hUCBSC: 0.03 ± 0.03, SCI: 0.07 ± 0.004, p < .001) was reduced and loss of lower motor neurons (MO-hUCBSC: 7.6 ± 0.43, SCI: 3 ± 0.12, p < .001) and astrogliosis density (MO-hUCBSC: 3.1 ± 0.15, SCI: 6.25 ± 1.42, p < 0.001) in the ventral horn of spinal cord were prevented in MO-hUCBSC group compared with SCI group. CONCLUSION: The results revealed that the combination of MO and hUCBSCs in comparison with the control group has neuroprotective effects in SCI.

Preoperative bowel preparation versus no preparation before spinal surgery: A randomised clinical trial.

AIMS AND OBJECTIVES: To investigate the effect of preoperative bowel preparation for patients undergoing spinal fusion surgery. BACKGROUND: Bowel preparation before major surgery is performed routinely to reduce the risk of postoperative complications related to gastrointestinal function. METHODS: A randomised clinical trial was performed that included forty-five elective spinal fusion patients allocated to one control group and two treatment groups. The patients received preoperative bowel preparation with enema, suppository or no bowel preparation. The outcome measures were defecation within 72 hours postoperatively, defecation on the fifth postoperative day, postoperative constipation, nausea, pain, well-being and ambulation. RESULTS: There were significant differences in favour of no bowel preparation compared with suppository group for the primary outcome; days to first defecation. There was a tendency for the patients who received no bowel preparation to recover from constipation more quickly than patients in the bowel preparation groups. The majority of patients did not defecate until the fourth postoperative day. CONCLUSIONS: This randomised study found no benefit from bowel preparation before major spine surgery on gastrointestinal function. The use of bowel preparation is not evidence-based and not performing it should be considered before major spine surgery until the effect is known.

Neurogenic bladder: Highly selective rhizotomy of specific dorsal rootlets maybe a better choice.

Spinal cord injury results not only in motor and sensory dysfunctions, but also in loss of normal urinary bladder functions. A number of clinical studies were focused on the strategies for improvement of functions of the bladder. Completely dorsal root rhizotomy or selective specific S2-4 dorsal root rhizotomy suppress autonomic hyper-reflexia but have the same defects: it could cause detrusor and sphincter over-relaxation and loss of reflexive erection in males. So precise operation needs to be considered. We designed an experimental trail to test the possibility on the basis of previous study. We found that different dorsal rootlets which conduct impulses from the detrusor or sphincter can be distinguished by electro-stimulation in SD rats. Highly selective rhizotomy of specific dorsal rootlets could change the intravesical pressure and urethral perfusion pressure respectively. We hypothese that for neurogenic bladder following spinal cord injury, highly selective rhizotomy of specific dorsal rootlets maybe improve the bladder capacity and the detrusor sphincter dyssynergia, and at the same time, the function of other pelvic organ could be maximize retainment.

Phrenic Nerve Stimulation: Technology and Clinical Applications.

Phrenic nerve stimulation is a technique used to reanimate the diaphragm of patients with central nervous system etiologies of respiratory insufficiency. Current clinical indications include congenital central hypoventilation syndrome, spinal cord injury above C4, brain stem injury, and idiopathic severe sleep apnea. Presurgical evaluation ensures proper patient selection by validating the intact circuit from the phrenic nerve through alveolar oxygenation. The procedure involves placing leads around the phrenic nerves bilaterally and attaching these leads to radio receivers in a subcutaneous pocket. The rate and amplitude of the current is adjusted via an external radio transmitter. After implantation, each patient progresses through a conditioning phase that strengthens the diaphragm and progressively provides independence from the mechanical ventilator. Studies indicate that patients and families experience an improved quality of life and are satisfied with the results. Phrenic nerve stimulation provides a safe and effective means for reanimating the diaphragm for certain patients with respiratory insufficiency, providing independence from mechanical ventilation.

A cost-utility analysis of sacral anterior root stimulation (SARS) compared with medical treatment in patients with complete spinal cord injury with a neurogenic bladder.

BACKGROUND CONTEXT: Sacral anterior root stimulation (SARS) and posterior sacral rhizotomy restores the ability to urinate on demand with low residual volumes, which is a key for preventing urinary complications that account for 10% of the causes of death in patients with spinal cord injury with a neurogenic bladder. Nevertheless, comparative cost-effectiveness results on a long time horizon are lacking to adequately inform decisions of reimbursement. PURPOSE: This study aimed to estimate the long-term cost-utility of SARS using the Finetech-Brindley device compared with medical treatment (anticholinergics+catheterization). STUDY DESIGN/SETTINGS: The following study design is used for the paper: Markov model elaborated with a 10-year time horizon; with four irreversible states: (1) initial treatment, (2) year 1 of surgery for urinary complication, (3) year >1 of surgery for urinary complication, and (4) death; and reversible states: urinary calculi; Finetech-Brindley device failures. PATIENT SAMPLE: The sample consisted of theoretical cohorts of patients with a complete spinal cord lesion since ≥1 year, and a neurogenic bladder. OUTCOME MEASURES: Effectiveness was expressed as quality adjusted life years (QALYs). Costs were valued in EUR 2013 in the perspective of the French health system. METHODS: A systematic review and meta-analyses were performed to estimate transition probabilities and QALYs. Costs were estimated from the literature, and through simulations using the 2013 French prospective payment system classification. Probabilistic analyses were conducted to handle parameter uncertainty. RESULTS: In the base case analysis (2.5% discount rate), the cost-utility ratio was 12,710 EUR per QALY gained. At a threshold of 30,000 EUR per QALY the probability of SARS being cost-effective compared with medical treatment was 60%. If the French Healthcare System reimbursed SARS for 80 patients per year during 10 years (anticipated target population), the expected incremental net health benefit would be 174 QALYs, and the expected value of perfect information (EVPI) would be 4.735 million EUR. The highest partial EVPI is reached for utility values and costs (1.3-1.6 million EUR). CONCLUSIONS: Our model shows that SARS using Finetech-Brindley device offers the most important benefit and should be considered cost-effective at a cost-effectiveness threshold of 30,000 EUR per QALY. Despite a high uncertainty, EVPI and partial EVPI may indicate that further research would not be profitable to inform decision-making.

An Active Learning Algorithm for Control of Epidural Electrostimulation.

Epidural electrostimulation has shown promise for spinal cord injury therapy. However, finding effective stimuli on the multi-electrode stimulating arrays employed requires a laborious manual search of a vast space for each patient. Widespread clinical application of these techniques would be greatly facilitated by an autonomous, algorithmic system which choses stimuli to simultaneously deliver effective therapy and explore this space. We propose a method based on GP-BUCB, a Gaussian process bandit algorithm. In n = 4 spinally transected rats, we implant epidural electrode arrays and examine the algorithm's performance in selecting bipolar stimuli to elicit specified muscle responses. These responses are compared with temporally interleaved intra-animal stimulus selections by a human expert. GP-BUCB successfully controlled the spinal electrostimulation preparation in 37 testing sessions, selecting 670 stimuli. These sessions included sustained autonomous operations (ten-session duration). Delivered performance with respect to the specified metric was as good as or better than that of the human expert. Despite receiving no information as to anatomically likely locations of effective stimuli, GP-BUCB also consistently discovered such a pattern. Further, GP-BUCB was able to extrapolate from previous sessions' results to make predictions about performance in new testing sessions, while remaining sufficiently flexible to capture temporal variability. These results provide validation for applying automated stimulus selection methods to the problem of spinal cord injury therapy.

Electroacupuncture promotes the differentiation of transplanted bone marrow mesenchymal stem cells overexpressing TrkC into neuron-like cells in transected spinal cord of rats.

Our previous study indicated that electroacupuncture (EA) could increase neurotrophin-3 (NT-3) levels in the injured spinal cord, stimulate the differentiation of transplanted bone marrow mesenchymal stem cells (MSCs), and improve functional recovery in the injured spinal cord of rats. However, the number of neuron-like cells derived from the MSCs is limited. It is known that NT-3 promotes the survival and differentiation of neurons by preferentially binding to its receptor TrkC. In this study, we attempted to transplant TrkC gene-modified MSCs (TrkC-MSCs) into the spinal cord with transection to investigate whether EA treatment could promote NT-3 secretion in the injured spinal cord and to determine whether increased NT-3 could further enhance transplanted MSCs overexpressing TrkC to differentiate into neuron-like cells, resulting in increased axonal regeneration and functional improvement in the injured spinal cord. Our results showed that EA increased NT-3 levels; furthermore, it promoted neuron-phenotype differentiation, synaptogenesis, and myelin formation of transplanted TrkC-MSCs. In addition, TrkC-MSC transplantation combined with EA (the TrkC-MSCs + EA group) treatment promoted the growth of the descending BDA-labeled corticospinal tracts (CSTs) and 5-HT-positive axonal regeneration across the lesion site into the caudal cord. In addition, the conduction of cortical motor-evoked potentials (MEPs) and hindlimb locomotor function increased as compared to controls (treated with the LacZ-MSCs, TrkC-MSCs, and LacZ-MSCs + EA groups). In the TrkC-MSCs + EA group, the injured spinal cord also showed upregulated expression of the proneurogenic factors laminin and GAP-43 and downregulated GFAP and chondroitin sulfate proteoglycans (CSPGs), major inhibitors of axonal growth. Together, our data suggest that TrkC-MSC transplantation combined with EA treatment spinal cord injury not only increased MSC survival and differentiation into neuron-like cells but also promoted CST regeneration across injured sites to the caudal cord and functional improvement, perhaps due to increase of NT-3 levels, upregulation of laminin and GAP-43, and downregulation of GFAP and CSPG proteins.

Surgical treatments to restore function control in spinal cord injury.

People with spinal cord injury (SCI) have a profound loss of control of their lives and abilities. Surgical procedures are of significant benefit in improving autonomy, self-care, and body function. Functional electrical stimulation (FES) is useful at higher levels of paralysis such as ASIA C5 or C6 where there are no remaining voluntary muscles for tendon transfer and can partially replace respiration, balance, and ambulation. Outcomes studies show that surgical care improves independence, strength of grasp, and measured quality of life. Those with tetraplegia should be referred for consultation for surgical reconstruction, release of contractures, consideration for neuroprostheses, and reconstruction.