Effect of pelvic laparoscopic implantation of neuroprosthesis in spinal cord injured subjects: a 1-year prospective randomized controlled study

Abstract Study design 1-year prospective RCT. Objective Examine the effect of implantable pulse generator and low-frequency stimulation of the pelvic nerves using laparoscopic implantation of neuroprosthesis (LION) compared with neuromuscular electrical stimulation (NMES) in SCI. Methods Inclusion criteria: traumatic spinal cord injury (SCI), age 18–55 years, neurological level-of-injury Th4–L1, time-since-injury >1 year, and AIS-grades A–B. Participants were randomized to (A) LION procedure or (B) control group receiving NMES. Primary outcome measure: Walking Index for Spinal Cord Injury (WISCI-II), which is a SCI specific outcome measure assessing ability to ambulate. Secondary outcome measures: Spinal Cord Independence Measure III (SCIM III), Patient Global Impression of Change (PGIC), Penn Spasm Frequency Scale (PSFS), severity of spasticity measured by Numeric Rating Scale (NRS-11); International Spinal Cord Injury data sets-Quality of Life Basic Data Set (QoLBDS), and Brief Pain Inventory (BPI). Results Seventeen SCI individuals, AIS grade A, neurological level ranging from Th4–L1, were randomized to the study. One individual was excluded prior to intervention. Eight participants (7 males) with a mean age (SD) of 35.5 (12.4) years were allocated to the LION procedure, 8 participants (7 males) with age of 38.8 (15.1) years were allocated to NMES. Significantly, 5 LION group participants gained 1 point on the WISCI II scale, (p < 0.013; Fisher´s exact test). WISCI II scale score did not change in controls. No significant changes were observed in the secondary outcome measures. Conclusion The LION procedure is a promising new treatment for individuals with SCI with significant one-year improvement in walking ability.

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Effects of exercise interventions on cardiovascular health in individuals with chronic, motor complete spinal cord injury: protocol for a randomised controlled trial [Cardiovascular Health/Outcomes: Improvements Created by Exercise and education in SCI (CHOICES) Study]

BMJ Open ◽

10.1136/bmjopen-2018-023540 ◽

2019 ◽

Vol 9 (1) ◽

pp. e023540 ◽

Cited By ~ 7

Author(s):

Andrei V Krassioukov ◽

Katharine D Currie ◽

Michèle Hubli ◽

Tom E Nightingale ◽

Abdullah A Alrashidi ◽

...

Keyword(s):

Physical Activity ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Arterial Stiffness ◽

Outcome Measures ◽

Cardiovascular Health ◽

Secondary Outcome ◽

Exercise Interventions ◽

Cord Injury ◽

Randomised Controlled

IntroductionRecent studies demonstrate that cardiovascular diseases and associated complications are the leading cause of morbidity and mortality in individuals with spinal cord injury (SCI). Abnormal arterial stiffness, defined by a carotid–to-femoral pulse wave velocity (cfPWV) ≥10 m/s, is a recognised risk factor for heart disease in individuals with SCI. There is a paucity of studies assessing the efficacy of conventional training modalities on arterial stiffness and other cardiovascular outcomes in this population. Therefore, this study aims to compare the efficacy of arm cycle ergometry training (ACET) and body weight-supported treadmill training (BWSTT) on reducing arterial stiffness in individuals with chronic motor complete, high-level (above the sixth thoracic segment) SCI.Methods and analysisThis is a multicentre, randomised, controlled, clinical trial. Eligible participants will be randomly assigned (1:1) into either ACET or BWSTT groups. Sixty participants with chronic (>1 year) SCI will be recruited from three sites in Canada (Vancouver, Toronto and Hamilton). Participants in each group will exercise three times per week up to 30 min and 60 min for ACET and BWSTT, respectively, over the period of 6 months. The primary outcome measure will be change in arterial stiffness (cfPWV) from baseline. Secondary outcome measures will include comprehensive assessments of: (1) cardiovascular parameters, (2) autonomic function, (3) body composition, (4) blood haematological and metabolic profiles, (5) cardiorespiratory fitness and (6) quality of life (QOL) and physical activity outcomes. Outcome measures will be assessed at baseline, 3 months, 6 months and 12 months (only QOL and physical activity outcomes). Statistical analyses will apply linear-mixed modelling to determine the training (time), group (ACET vs BWSTT) and interaction (time × group) effects on all outcomes.Ethics and disseminationEthical approval was obtained from all three participating sites. Primary and secondary outcome data will be submitted for publication in peer-reviewed journals and widely disseminated.Trial registration numberNCT01718977; Pre-results.Trial statusRecruitment for this study began on January 2013 and the first participant was randomized on April 2013. Recruitment stopped on October 2018.

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Walking Ability Outcome Measures in Individuals with Spinal Cord Injury: A Systematic Review

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18189517 ◽

2021 ◽

Vol 18 (18) ◽

pp. 9517

Author(s):

Isabel Sinovas-Alonso ◽

Ángel Gil-Agudo ◽

Roberto Cano-de-la-Cuerda ◽

Antonio J. del-Ama

Keyword(s):

Systematic Review ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Outcome Measures ◽

Berg Balance Scale ◽

Walking Ability ◽

Walk Test ◽

Timed Up And Go ◽

Cord Injury ◽

Profile Score

Walking function recovery in spinal cord injury (SCI) is tackled through several therapeutic approaches in which precise evaluation is essential. A systematic review was performed to provide an updated qualitative review of walking ability outcome measures in SCI and to analyze their psychometric properties. PubMed, Cochrane, and PEDro databases were consulted until 1 April 2020. Seventeen articles written in English were included. Five of them studied the walking index for SCI, four studied the 10 meter walk test, and two studied the six-minute walk test, the timed Up and go test, and the Berg balance scale. The rest of the articles studied the following metrics: gait profile score, spinal cord injury functional ambulation profile, five times sit-to-stand test, spinal cord injury functional ambulation inventory, spinal cord independence measure (indoors and outdoors mobility items), locomotor stages in spinal cord injury, community balance and mobility scale, and activity-based balance level evaluation scale. The choice of a single or a set of metrics should be determined by the clinician. Based on the results obtained in this review, a combination of outcome measures is proposed to assess walking ability. Future work is required to integrate a more realistic environment for walking assessment.

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The development of an outcome measures toolkit for spinal cord injury rehabilitation

Canadian Journal of Occupational Therapy ◽

10.1177/0008417417690170 ◽

2017 ◽

Vol 84 (2) ◽

pp. 119-129 ◽

Cited By ~ 3

Author(s):

Christie W. L. Chan ◽

William C. Miller ◽

Matthew Querée ◽

Vanessa K. Noonan ◽

Dalton L. Wolfe ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Clinical Practice ◽

Outcome Measures ◽

Best Practice ◽

Outcome Measure ◽

Medical Condition ◽

Measurement Properties ◽

Injury Rehabilitation ◽

Cord Injury

Background. Spinal cord injury (SCI) is a complex medical condition that can be difficult to monitor. Purpose. This study aimed to establish a common set of validated outcome measures specifically for SCI clinical practice. Method. In a three-round online Delphi process, experts in SCI care across Canada suggested and ranked outcome measures for clinical practice. The facilitators provided feedback between rounds and determined if consensus (at least 75% agreement) was reached on a single outcome measure per clinical area. Findings. One hundred and forty-eight outcome measures were initially considered for inclusion. After three rounds, consensus was reached for 23 out of 30 clinical areas. In the remaining seven, more than one outcome measure was recommended. The final toolkit comprises 33 outcome measures with sufficient measurement properties for use with a SCI population. Implications. An outcome measures toolkit validated specifically for SCI should lead to improved identification of best practice and enable clinicians to monitor client progress effectively.

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Electrophysiological Outcome Measures in Spinal Cord Injury Clinical Trials: A Systematic Review

Topics in Spinal Cord Injury Rehabilitation ◽

10.1310/sci2504-340 ◽

2019 ◽

Vol 25 (4) ◽

pp. 340-354

Author(s):

Radha Korupolu ◽

Argyrios Stampas ◽

Mani Singh ◽

Ping Zhou ◽

Gerard Francisco

Keyword(s):

Systematic Review ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Clinical Trials ◽

Evoked Potentials ◽

Outcome Measures ◽

Outcome Measure ◽

Silent Period ◽

Contact Heat Evoked Potentials ◽

Cord Injury

Background: Electrophysiological measures are being increasingly utilized due to their ability to provide objective measurements with minimal bias and to detect subtle changes with quantitative data on neural function. Heterogeneous reporting of trial outcomes limits effective interstudy comparison and optimization of treatment. Objective: The objective of this systematic review is to describe the reporting of electrophysiological outcome measures in spinal cord injury (SCI) clinical trials in order to inform a subsequent consensus study. Methods: A systematic search of PubMed and EMBASE databases was conducted according to PRISMA guidelines. Adult human SCI clinical trials published in English between January 1, 2008 and September 15, 2018 with at least one electrophysiological outcome measure were eligible. Findings were reviewed by all authors to create a synthesis narrative describing each outcome measure. Results: Sixty-four SCI clinical trials were included in this review. Identified electrophysiological outcomes included electromyography activity (44%), motor evoked potentials (33%), somatosensory evoked potentials (33%), H-reflex (20%), reflex electromyography activity (11%), nerve conduction studies (9%), silent period (3%), contact heat evoked potentials (2%), and sympathetic skin response (2%). Heterogeneity was present in regard to both methods of measurement and reporting of electrophysiological outcome measures. Conclusion: This review demonstrates need for the development of a standardized reporting set for electrophysiological outcome measures. Limitations of this review include exclusion of non-English publications, studies more than 10 years old, and an inability to assess methodological quality of primary studies due to a lack of guidelines on reporting of systematic reviews of outcome measures.

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Exercise Ameliorates Spinal Cord Injury by Changing DNA Methylation

Cells ◽

10.3390/cells10010143 ◽

2021 ◽

Vol 10 (1) ◽

pp. 143

Author(s):

Ganchimeg Davaa ◽

Jin Young Hong ◽

Tae Uk Kim ◽

Seong Jae Lee ◽

Seo Young Kim ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Cortex ◽

Functional Recovery ◽

Treadmill Exercise ◽

Exercise Group ◽

Control Group ◽

Epigenetic Changes ◽

Cord Injury ◽

The Brain

Exercise training is a traditional method to maximize remaining function in patients with spinal cord injury (SCI), but the exact mechanism by which exercise promotes recovery after SCI has not been identified; whether exercise truly has a beneficial effect on SCI also remains unclear. Previously, we showed that epigenetic changes in the brain motor cortex occur after SCI and that a treatment leading to epigenetic modulation effectively promotes functional recovery after SCI. We aimed to determine how exercise induces functional improvement in rats subjected to SCI and whether epigenetic changes are engaged in the effects of exercise. A spinal cord contusion model was established in rats, which were then subjected to treadmill exercise for 12 weeks. We found that the size of the lesion cavity and the number of macrophages were decreased more in the exercise group than in the control group after 12 weeks of injury. Immunofluorescence and DNA dot blot analysis revealed that levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the brain motor cortex were increased after exercise. Accordingly, the expression of ten-eleven translocation (Tet) family members (Tet1, Tet2, and Tet3) in the brain motor cortex also elevated. However, no macrophage polarization was induced by exercise. Locomotor function, including Basso, Beattie, and Bresnahan (BBB) and ladder scores, also improved in the exercise group compared to the control group. We concluded that treadmill exercise facilitates functional recovery in rats with SCI, and mechanistically epigenetic changes in the brain motor cortex may contribute to exercise-induced improvements.

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Using a saddle-assistive device equipped with mechanical orthosis for walking of the person with incomplete spinal cord injury

Proceedings of the Institution of Mechanical Engineers Part H Journal of Engineering in Medicine ◽

10.1177/09544119211020146 ◽

2021 ◽

pp. 095441192110201

Author(s):

Akbar Hojjati Najafabadi ◽

Saeid Amini ◽

Farzam Farahmand

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Reaction Force ◽

Assistive Devices ◽

Assistive Device ◽

Walking Ability ◽

Vertical Force ◽

Incomplete Spinal Cord Injury ◽

Combined Application ◽

Cord Injury

The majority of the people with incomplete spinal cord injury lose their walking ability, due to the weakness of their muscle motors in providing torque. As a result, developing assistive devices to improve their conditionis of great importance. In this study, a combined application of the saddle-assistive device (S-AD) and mechanical medial linkage or thosis was evaluated to improve the walking ability in patients with spinal cord injury in the gait laboratory. This mobile assistive device is called the saddle-assistive device equipped with medial linkage or thosis (S-ADEM). In this device, a mechanical orthosis was used in a wheeled walker as previously done in the literature. Initially, for evaluation of the proposed assistive device, the experimental results related to the forces and torques exerted on the feet and upper limbs of a person with the incomplete Spinal Cord Injury (SCI) during walking usingthe standard walker were compared with an those obtained from using the S-ADEM on an able-bodied subject. It was found that using this combination of assistive devices decreases the vertical force and torque on the foot at the time of walking by 53% and 48%, respectively compared to a standard walker. Moreover, the hand-reaction force on the upper limb was negligible instanding and walking positions usingthe introduced device. The findings of this study revealed that the walking ability of the patients with incomplete SCI was improved using the proposed device, which is due to the bodyweight support and the motion technology used in it.

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AAV2-mediated and hypoxia response element-directed expression of bFGF in neural stem cells showed therapeutic effects on spinal cord injury in rats

Cell Death and Disease ◽

10.1038/s41419-021-03546-6 ◽

2021 ◽

Vol 12 (3) ◽

Author(s):

Sipin Zhu ◽

Yibo Ying ◽

Jiahui Ye ◽

Min Chen ◽

Qiuji Wu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Clinical Trials ◽

Control Group ◽

Therapeutic Effects ◽

Hypoxia Response Element ◽

Neurofilament Protein ◽

Response Element ◽

Hypoxia Response ◽

Cord Injury

AbstractNeural stem cell (NSCs) transplantation has been one of the hot topics in the repair of spinal cord injury (SCI). Fibroblast growth factor (FGF) is considered a promising nerve injury therapy after SCI. However, owing to a hostile hypoxia condition in SCI, there remains a challenging issue in implementing these tactics to repair SCI. In this report, we used adeno-associated virus 2 (AAV2), a prototype AAV used in clinical trials for human neuron disorders, basic FGF (bFGF) gene under the regulation of hypoxia response element (HRE) was constructed and transduced into NSCs to yield AAV2-5HRE-bFGF-NSCs. Our results showed that its treatment yielded temporally increased expression of bFGF in SCI, and improved scores of functional recovery after SCI compared to vehicle control (AAV2-5HRE-NSCs) based on the analyses of the inclined plane test, Basso–Beattie–Bresnahan (BBB) scale and footprint analysis. Mechanistic studies showed that AAV2-5HRE-bFGF-NSCs treatment increased the expression of neuron-specific neuronal nuclei protein (NeuN), neuromodulin GAP43, and neurofilament protein NF200 while decreased the expression of glial fibrillary acidic protein (GFAP) as compared to the control group. Further, the expressions of autophagy-associated proteins LC3-II and Beclin 1 were decreased, whereas the expression of P62 protein was increased in AAV2-5HRE-bFGF-NSCs treatment group. Taken together, our data indicate that AAV2-5HRE-bFGF-NSCs treatment improved the recovery of SCI rats, which is accompanied by evidence of nerve regeneration, and inhibition of SCI-induced glial scar formation and cell autophagy. Thus, this study represents a step forward towards the potential use of AAV2-5HRE-bFGF-NSCs for future clinical trials of SCI repair.

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The Effect of Exoskeletal-Assisted Walking on Spinal Cord Injury Bowel Function: Results from a Randomized Trial and Comparison to Other Physical Interventions

Journal of Clinical Medicine ◽

10.3390/jcm10050964 ◽

2021 ◽

Vol 10 (5) ◽

pp. 964

Author(s):

Peter H. Gorman ◽

Gail F. Forrest ◽

Pierre K. Asselin ◽

William Scott ◽

Stephen Kornfeld ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Bowel Function ◽

Bowel Dysfunction ◽

Secondary Outcome ◽

Secondary Outcome Measure ◽

Cord Injury ◽

Patient Reported ◽

Stool Form ◽

Time Since Injury

Bowel function after spinal cord injury (SCI) is compromised because of a lack of voluntary control and reduction in bowel motility, often leading to incontinence and constipation not easily managed. Physical activity and upright posture may play a role in dealing with these issues. We performed a three-center, randomized, controlled, crossover clinical trial of exoskeletal-assisted walking (EAW) compared to usual activity (UA) in people with chronic SCI. As a secondary outcome measure, the effect of this intervention on bowel function was assessed using a 10-question bowel function survey, the Bristol Stool Form Scale (BSS) and the Spinal Cord Injury Quality of Life (SCI-QOL) Bowel Management Difficulties instrument. Fifty participants completed the study, with bowel data available for 49. The amount of time needed for the bowel program on average was reduced in 24% of the participants after EAW. A trend toward normalization of stool form was noted. There were no significant effects on patient-reported outcomes for bowel function for the SCI-QOL components, although the time since injury may have played a role. Subset analysis suggested that EAW produces a greater positive effect in men than women and may be more effective in motor-complete individuals with respect to stool consistency. EAW, along with other physical interventions previously investigated, may be able to play a previously underappreciated role in assisting with SCI-related bowel dysfunction.

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Spinal Cord Tissue Bridges Validation Study: Predictive Relationships With Sensory Scores Following Cervical Spinal Cord Injury

Topics in Spinal Cord Injury Rehabilitation ◽

10.46292/sci21-00018 ◽

2021 ◽

Author(s):

Andrew C. Smith ◽

Denise R. O’Dell ◽

Wesley A. Thornton ◽

David Dungan ◽

Eli Robinson ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

External Validation ◽

Inpatient Rehabilitation ◽

Spinal Cord Tissue ◽

Light Touch ◽

Post Injury ◽

Data Set ◽

Cord Injury ◽

Predictive Relationships

Background: Using magnetic resonance imaging (MRI), widths of ventral tissue bridges demonstrated significant predictive relationships with future pinprick sensory scores, and widths of dorsal tissue bridges demonstrated significant predictive relationships with future light touch sensory scores, following spinal cord injury (SCI). These studies involved smaller participant numbers, and external validation of their findings is warranted. Objectives: The purpose of this study was to validate these previous findings using a larger independent data set. Methods: Widths of ventral and dorsal tissue bridges were quantified using MRI in persons post cervical level SCI (average 3.7 weeks post injury), and pinprick and light touch sensory scores were acquired at discharge from inpatient rehabilitation (average 14.3 weeks post injury). Pearson product-moments were calculated and linear regression models were created from these data. Results: Wider ventral tissue bridges were significantly correlated with pinprick scores (r = 0.31, p < 0.001, N = 136) and wider dorsal tissue bridges were significantly correlated with light touch scores (r = 0.31, p < 0.001, N = 136) at discharge from inpatient rehabilitation. Conclusion: This retrospective study’s results provide external validation of previous findings, using a larger sample size. Following SCI, ventral tissue bridges hold significant predictive relationships with future pinprick sensory scores and dorsal tissue bridges hold significant predictive relationships with future light touch sensory scores.

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Transplantation of Neural Stem/Progenitor Cells at Different Locations in Mice with Spinal Cord Injury

Cell Transplantation ◽

10.3727/096368913x670967 ◽

2014 ◽

Vol 23 (11) ◽

pp. 1451-1464 ◽

Cited By ~ 21

Author(s):

Hiroki Iwai ◽

Satoshi Nori ◽

Soraya Nishimura ◽

Akimasa Yasuda ◽

Morito Takano ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Progenitor Cells ◽

Functional Recovery ◽

Control Group ◽

Cord Injury ◽

Neural Stem Progenitor Cells ◽

Neurotropic Factor ◽

Transplantation Site

Transplantation of neural stem/progenitor cells (NS/PCs) promotes functional recovery after spinal cord injury (SCI); however, few studies have examined the optimal site of NS/PC transplantation in the spinal cord. The purpose of this study was to determine the optimal transplantation site of NS/PCs for the treatment of SCI. Wild-type mice were generated with contusive SCI at the T10 level, and NS/PCs were derived from fetal transgenic mice. These NS/PCs ubiquitously expressed ffLuc-cp156 protein (Venus and luciferase fusion protein) and so could be detected by in vivo bioluminescence imaging 9 days postinjury. NS/PCs (low: 250,000 cells per mouse; high: 1 million cells per mouse) were grafted into the spinal cord at the lesion epicenter (E) or at rostral and caudal (RC) sites. Phosphate-buffered saline was injected into E as a control. Motor functional recovery was better in each of the transplantation groups (E-Low, E-High, RC-Low, and RC-High) than in the control group. The photon counts of the grafted NS/PCs were similar in each of the four transplantation groups, suggesting that the survival of NS/PCs was fairly uniform when more than a certain threshold number of cells were transplanted. Quantitative RT-PCR analyses demonstrated that brain-derived neurotropic factor expression was higher in the RC segment than in the E segment, and this may underlie why NS/PCs more readily differentiated into neurons than into astrocytes in the RC group. The location of the transplantation site did not affect the area of spared fibers, angiogenesis, or the expression of any other mediators. These findings indicated that the microenvironments of the E and RC sites are able to support NS/PCs transplanted during the subacute phase of SCI similarly. Optimally, a certain threshold number of NS/PCs should be grafted into the E segment to avoid damaging sites adjacent to the lesion during the injection procedure.

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