From Toxin to Treatment: A Narrative Review on the Use of Botulinum Toxin for Autonomic Dysfunction.

Since its regulatory approval over a half-century ago, botulinum toxin has evolved from one of the most potent neurotoxins known to becoming routinely adopted in clinical practice. Botulinum toxin, a highly potent neurotoxin produced by Clostridium botulinum, can cause botulism illness, characterized by widespread muscle weakness due to inhibition of acetylcholine transmission at neuromuscular junctions. The observation of botulinum toxin's anticholinergic properties led to the investigation of its potential benefits for conditions with an underlying etiology of cholinergic transmission, including autonomic nervous system dysfunction. These conditions range from disorders of the integument to gastrointestinal and urinary systems. Several formulations of botulinum toxin have been developed and tested over time, significantly increasing the availability of this treatment for appropriate clinical use. Despite the accelerated and expanded use of botulinum toxin, there lacks an updated comprehensive review on its therapeutic use, particularly to treat autonomic dysfunction. This narrative review provides an overview of the effect of botulinum toxin in the treatment of autonomic dysfunction and summarizes the different formulations and dosages most widely studied, while highlighting reported outcomes and the occurrence of any adverse events.

Web-Based Information on Spinal Cord Stimulation: Qualitative Assessment of Publicly Accessible Online Resources.

BACKGROUND: Despite the growing accessibility of web-based information related to spinal cord stimulation (SCS), the content and quality of commonly encountered websites remain unknown. OBJECTIVE: This study aimed to assess the content and quality of web-based information on SCS. METHODS: This qualitative study was prospectively registered in Open Science Framework. Google Trends was used to identify the top trending, SCS-related search queries from 2012 to 2022. Top queried terms were then entered into separate search engines. Information found on websites within the first 2 pages of results was extracted and assessed for quality using the DISCERN instrument, the Journal of the American Medical Association benchmark criteria, and the Health on the Net Foundation code of conduct certification. Website readability and SCS-related information were also assessed. RESULTS: After exclusions, 42 unique sites were identified (scientific resources: n=6, nonprofit: n=12, for-profit: n=20, news or media: n=2, and personal or blog: n=2). Overall, information quality was moderate (DISCERN). Few sites met all the Journal of the American Medical Association benchmark criteria (n=3, 7%) or had Health on the Net Foundation certification (n=7, 16%). On average, information was difficult to read, requiring a 9th- to 10th-grade level of reading comprehension. Sites described SCS subcategories (n=14, 33%), indications (n=38, 90%), contraindications (n=14, 33%), side effects or risks (n=28, 66%), device considerations (n=25, 59%), follow-up (n=22, 52%), expected outcomes (n=31, 73%), provided authorship details (n=20, 47%), and publication dates (n=19, 45%). The proportion of for-profit sites reporting authorship information was comparatively less than other site types (n=3, 15%). Almost all sites focused on surgically implanted SCS (n=37, 88%). On average, nonprofit sites contained the greatest number of peer-reviewed reference citations (n=6, 50%). For-profit sites showed the highest proportion of physician or clinical referrals among site types (n=17, 85%) indicating implicit bias (ie, auto-referral). CONCLUSIONS: Overall, our findings suggest the public may be exposed to incomplete or dated information from unidentifiable sources that could put consumers and patient groups at risk.

REPORT-SCS: minimum reporting standards for spinal cord stimulation studies in spinal cord injury.

Objective.Electrical spinal cord stimulation (SCS) has emerged as a promising therapy for recovery of motor and autonomic dysfunctions following spinal cord injury (SCI). Despite the rise in studies using SCS for SCI complications, there are no standard guidelines for reporting SCS parameters in research publications, making it challenging to compare, interpret or reproduce reported effects across experimental studies.Approach.To develop guidelines for minimum reporting standards for SCS parameters in pre-clinical and clinical SCI research, we gathered an international panel of expert clinicians and scientists. Using a Delphi approach, we developed guideline items and surveyed the panel on their level of agreement for each item.Main results.There was strong agreement on 26 of the 29 items identified for establishing minimum reporting standards for SCS studies. The guidelines encompass three major SCS categories: hardware, configuration and current parameters, and the intervention.Significance.Standardized reporting of stimulation parameters will ensure that SCS studies can be easily analyzed, replicated, and interpreted by the scientific community, thereby expanding the SCS knowledge base and fostering transparency in reporting.

Heart Rate Variability-Based Prediction of Autonomic Dysreflexia After Spinal Cord Injury.

Autonomic dysreflexia (AD) is a common autonomic complication of spinal cord injury (SCI) characterized by a sudden increase is blood pressure triggered by peripheral stimulation, such as bladder distention. Iatrogenic AD events often occur during various medical procedures including urodynamic assessments (UDSs) used to evaluate lower urinary tract (LUT) function in individuals with SCI. To date, there are no established clinical practices that would allow early detection of the development of episodes of AD. Heart rate variability (HRV) is a reliable and non-invasive metric for evaluating autonomic regulation of the cardiovascular system, with demonstrated utility in people with SCI during UDSs. We aim to provide a comprehensive evaluation of cardiovascular function during UDS-induced AD using ultra-short-term HRV analysis and identify changes in cardiovascular dynamics to predict the onset of AD. We assessed cardiovascular data in a total of 24 participants with sensorimotor complete SCI above T6 (17 males, 7 females, median age = 43 [36-50] years) who experienced AD during UDS. We used continuous electrocardiographic recordings to evaluate HRV in 60 sec overlapping windows during filling cystometry. The mean of "normal-to-normal" heartbeats (meanNN), its standard deviation (SDNN), and the root mean square of successive differences (RMSSD) were calculated and used in all subsequent analyses. We found that SDNN and RMSSD diminished during the early phase of bladder filling and sharply increased during AD. Using the lowest point of statistical variability in heart rate (i.e., SDNN), we were able to predict AD events within 240 sec (percentile 25-percentile 75: 172-339 sec) before the first systolic blood pressure peak after AD onset (sensitivity = 0.667; specificity = 0.875). Our results indicated a temporary increase in sympathetic activity during the early phase of bladder filling, which is followed by an increase in parasympathetic outflow to the heart when AD occurs. These findings have significant clinical implications that extend beyond the context of UDS and demonstrate the importance of identifying early changes in HRV in order to accurately predict AD episodes in people living with SCI.

A qualitative study of the perceived benefits of participating in a spinal cord rehabilitation intervention in a low-middle income country.

PURPOSE: Improving quality of life (QoL) is a major goal of rehabilitation following spinal cord injury (SCI). However, people with disabilities in resource constrained contexts have limited access to rehabilitation and poorer health outcomes, including QoL. There is a paucity of qualitative research on the experiences of persons with SCI involved in rehabilitation programmes in low-middle income countries. This study aimed to assess participants' perceptions of the benefits of a 24-week SCI rehabilitation programme delivered as part of a pilot randomized controlled trial (RCT) in South Africa. MATERIALS AND METHODS: Sixteen participants, with chronic motor-incomplete tetraplegia, were enrolled in a two-arm pilot RCT involving robotic locomotor training, a novel technology, and standard activity-based training (Pan African Clinical Trial Registry (PACTR201608001647143)). Data were collected via in-depth interviews and analysed using thematic analysis. RESULTS: Participants described several improvements in QoL, including enhanced functional independence; reduced secondary complications; and improved psychosocial and emotional well-being. CONCLUSIONS: The holistic approach to rehabilitation calls for the involvement of individuals' views about what matters to them to inform clinical practice and to highlight the role that physical activity and the perceived successes play in shaping the lived experiences after SCI. TRIAL REGISTRATION: Pan African Clinical Trial Registry (PACTR201608001647143), registration date (21st May 2016), study start date (30th Nov 2016)https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=1647.

Rehabilitation plays an integral role in prompting and integrating positive experiences and changes in QoL for people with spinal cord injury (SCI), especially in a resource constrained context where there is limited opportunity to participate in rehabilitation interventions.Locomotor training and activity-based training can enhance perceived functional independence and psychosocial well-being following SCI.Rather than focus on traditional physiological outcomes, rehabilitation interventions can address quality of life outcomes in order to improve well-being in a way that is meaningful to people with SCI.

Robotic locomotor training in a low-resource setting: a randomized pilot and feasibility trial.

PURPOSE: Activity-based Training (ABT) represents the current standard of neurological rehabilitation. Robotic Locomotor Training (RLT), an innovative technique, aims to enhance rehabilitation outcomes. This study aimed to conduct a randomized pilot and feasibility trial of a locomotor training program within South Africa. MATERIALS AND METHODS: Individuals with chronic traumatic motor incomplete tetraplegia (n = 16). Each intervention involved 60-minute sessions, 3x per week, for 24-weeks. Outcomes included feasibility measures and functional capacity. RESULTS: 17 out of 110 individuals initiated the program (recruitment rate = 15.4%) and 16 completed the program (drop-out rate = 5.8%) and attended sessions (attendance rate = 93.9%). Both groups showed a significant increase in upper extremity motor score (MS) and abdominal strength post intervention. Only the RLT group showed a significant change in lower extremity MS, with a mean increase of 3.00 [0.00; 16.5] points over time. Distance walked in the Functional Ambulatory Inventory (SCI-FAI) increased significantly (p = 0.02) over time only for the RLT group. CONCLUSIONS: Feasibility rates of the intervention and functional outcomes justify a subsequent powered RCT comparing RLT to ABT as an effective rehabilitation tool for potentially improving functional strength and walking capacity in people with incomplete SCI.

Spinal cord injury causes severe limitations to functional capacity, independence, and quality of life.Robotic Locomotor Training is growing rehabilitation modality for people with spinal cord injury, but currently its effects on functional capacity are limited.In a relatively small sample, this study shows that large, randomized control trials are feasible within a low-income setting.The preliminary findings of this study show that 12 weeks of locomotor training can improve ambulatory function and functional strength in individuals with spinal cord injury.

The Microbiological Burden of Short-Term Catheter Reuse in Individuals with Spinal Cord Injury: A Prospective Study.

Despite the risk of developing catheter-associated urinary tract infections (CAUTI), catheter reuse is common among people with spinal cord injury (SCI). This study examined the microbiological burden and catheter surface changes associated with short-term reuse. Ten individuals with chronic SCI reused their catheters over 3 days. Urine and catheter swab cultures were collected daily for analysis. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) analyses were used to assess catheter surface changes. Catheter swab cultures showed no growth after 48 h (47.8%), skin flora (28.9%), mixed flora (17.8%), or bacterial growth (5.5%). Asymptomatic bacteriuria was found for most participants at baseline (n = 9) and all at follow-up (n = 10). Urine samples contained Escherichia coli (58%), Klebsiella pneumoniae (30%), Enterococcus faecalis (26%), Acinetobacter calcoaceticus-baumannii (10%), Pseudomonas aeruginosa (6%) or Proteus vulgaris (2%). Most urine cultures showed resistance to one or more antibiotics (62%). SEM images demonstrated structural damage, biofilm and/or bacteria on all reused catheter surfaces. XPS analyses also confirmed the deposition of bacterial biofilm on reused catheters. Catheter surface changes and the presence of antibiotic-resistant bacteria were evident following short-term reuse, which may increase susceptibility to CAUTI in individuals with SCI despite asymptomatic bacteriuria.

Motor and autonomic concomitant health improvements with neuromodulation and exercise (MACHINE) training: a randomised controlled trial in individuals with spinal cord injury.

INTRODUCTION: Motor and autonomic dysfunctions are widespread among people with spinal cord injury (SCI), leading to poor health and reduced quality of life. Exercise interventions, such as locomotor training (LT), can promote sensorimotor and autonomic recovery post SCI. Recently, breakthroughs in SCI research have reported beneficial effects of electrical spinal cord stimulation (SCS) on motor and autonomic functions. Despite literature supporting the independent benefits of transcutaneous SCS (TSCS) and LT, the effect of pairing TSCS with LT is unknown. These therapies are non-invasive, customisable and have the potential to simultaneously benefit both sensorimotor and autonomic functions. The aim of this study is to assess the effects of LT paired with TSCS in people with chronic SCI on outcomes of sensorimotor and autonomic function. METHODS AND ANALYSIS: Twelve eligible participants with chronic (>1 year) motor-complete SCI, at or above the sixth thoracic segment, will be enrolled in this single-blinded, randomised sham-controlled trial. Participants will undergo mapping for optimisation of stimulation parameters and baseline assessments of motor and autonomic functions. Participants will then be randomly assigned to either LT+TSCS or LT+Sham stimulation for 12 weeks, after which postintervention assessments will be performed to determine the effect of TSCS on motor and autonomic functions. The primary outcome of interest is attempted voluntary muscle activation using surface electromyography. The secondary outcomes relate to sensorimotor function, cardiovascular function, pelvic organ function and health-related quality of life. Statistical analysis will be performed using two-way repeated measures Analysis of variance (ANOVAs) or Kruskal-Wallis and Cohen's effect sizes. ETHICS AND DISSEMINATION: This study has been approved after full ethical review by the University of British Columbia's Research Ethics Board. The stimulator used in this trial has received Investigation Testing Authorisation from Health Canada. Trial results will be disseminated through peer-reviewed publications, conference presentations and seminars. TRIAL REGISTRATION NUMBER: NCT04726059.

Effect of epidural spinal cord stimulation on female sexual function after spinal cord injury.

Sexual dysfunction is a common consequence for women with spinal cord injury (SCI); however, current treatments are ineffective, especially in the under-prioritized population of women with SCI. This case-series, a secondary analysis of the Epidural Stimulation After Neurologic Damage (E-STAND) clinical trial aimed to investigate the effect of epidural spinal cord stimulation (ESCS) on sexual function and distress in women with SCI. Three females, with chronic, thoracic, sensorimotor complete SCI received daily (24 h/day) tonic ESCS for 13 months. Questionnaires, including the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) were collected monthly. There was a 3.2-point (13.2%) mean increase in total FSFI from baseline (24.5 ± 4.1) to post-intervention (27.8 ± 6.6), with a 4.8-50% improvement in the sub-domains of desire, arousal, orgasm and satisfaction. Sexual distress was reduced by 55%, with a mean decrease of 12 points (55.4%) from baseline (21.7 ± 17.2) to post-intervention (9.7 ± 10.8). There was a clinically meaningful change of 14 points in the International Standards for Neurological Classification of Spinal Cord Injury total sensory score from baseline (102 ± 10.5) to post-intervention (116 ± 17.4), without aggravating dyspareunia. ESCS is a promising treatment for sexual dysfunction and distress in women with severe SCI. Developing therapeutic interventions for sexual function is one of the most meaningful recovery targets for people with SCI. Additional large-scale investigations are needed to understand the long-term safety and feasibility of ESCS as a viable therapy for sexual dysfunction. Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03026816, NCT03026816.

Spinal Cord Stimulation Prevents Autonomic Dysreflexia in Individuals with Spinal Cord Injury: A Case Series.

Spinal cord injury (SCI) results in severe cardiovascular dysfunction due to the disruption of supraspinal control. Autonomic dysreflexia (AD), an uncontrolled rise in blood pressure in response to peripheral stimuli including common bowel routine, digital anorectal stimulation (DARS), reduces the quality of life, and increases morbidity and mortality. Recently, spinal cord stimulation (SCS) has emerged as a potential intervention to mitigate unstable blood pressure following SCI. The objective of this case series was to test the real-time effect of epidural SCS (eSCS) at the lumbosacral spinal cord, the most common implant location, on mitigating AD in individuals with SCI. We recruited three individuals with cervical and upper thoracic motor-complete SCI who have an implanted epidural stimulator. We demonstrated that eSCS can reduce the elevation in blood pressure and prevent DARS-induced AD. The blood pressure variability analysis indicated that eSCS potentially reduced vascular sympathetic nervous system activity during DARS, compared to without eSCS. This case series provides evidence to support the use of eSCS to prevent AD episodes during routine bowel procedures, improving the quality of life for individuals with SCI and potentially reducing cardiovascular risks.

Robotic locomotor training for spasticity, pain, and quality of life in individuals with chronic SCI: A pilot randomized controlled trial.

Objective: The prevention and treatment of secondary complications is a key priority for people with spinal cord injury and a fundamental goal of rehabilitation. Activity-based Training (ABT) and Robotic Locomotor Training (RLT) demonstrate promising results for reducing secondary complications associated with SCI. However, there is a need for increased evidence through randomized controlled trials. Therefore, we aimed to investigate the effect of RLT and ABT interventions on pain, spasticity, and quality of life in individuals with spinal cord injuries. Methods: Participants with chronic motor incomplete tetraplegia (n = 16) were recruited. Each intervention involved 60-minute sessions, 3× per week, over 24-weeks. RLT involved walking in an Ekso GT exoskeleton. ABT involved a combination of resistance, cardiovascular and weight-bearing exercise. Outcomes of interest included the Modified Ashworth Scale, the International SCI Pain Basic Data Set Version 2, and the International SCI Quality of Life Basic Data Set. Results: Neither intervention altered symptoms of spasticity. Pain intensity increased from pre-post intervention for both groups, with a mean increase of 1.55 [-0.82, 3.92] (p = 0.03) and 1.56 [-0.43, 3.55] (p = 0.02) points for the RLT and ABT group, respectively. The ABT group had an increase in pain interference scores of 100%, 50%, and 109% for the daily activity, mood, and sleep domain, respectively. The RLT group had an increase in pain interference scores of 86% and 69% for the daily activity and mood domain respectively, but no change in the sleep domain. The RLT group had increased perceptions of quality of life with changes of 2.37 [0.32, 4.41], 2.00 [0.43, 3.56] and 0.25 [-1.63, 2.13] points, p = 0.03, for the general, physical, and psychological domains, respectively. The ABT group had increased perceptions of general, physical and psychological quality of life with changes of 0.75 [-1.38, 2.88], 0.62 [-1.83, 3.07] and 0.63 [-1.87, 3.13] points, respectively. Conclusions: Despite increased pain ratings and no change in symptoms of spasticity, there was an increase in perceived quality of life for both groups over 24-weeks. This dichotomy warrants additional investigation in future large-scale randomized controlled trials.

Mapping the Iceberg of Autonomic Recovery: Mechanistic Underpinnings of Neuromodulation following Spinal Cord Injury.

Spinal cord injury leads to disruption in autonomic control resulting in cardiovascular, bowel, and lower urinary tract dysfunctions, all of which significantly reduce health-related quality of life. Although spinal cord stimulation shows promise for promoting autonomic recovery, the underlying mechanisms are unclear. Based on current preclinical and clinical evidence, this narrative review provides the most plausible mechanisms underlying the effects of spinal cord stimulation for autonomic recovery, including activation of the somatoautonomic reflex and induction of neuroplastic changes in the spinal cord. Areas where evidence is limited are highlighted in an effort to guide the scientific community to further explore these mechanisms and advance the clinical translation of spinal cord stimulation for autonomic recovery.

Effects of non-invasive spinal cord stimulation on lower urinary tract, bowel, and sexual functions in individuals with chronic motor-complete spinal cord injury: Protocol for a pilot clinical trial.

INTRODUCTION: Electrical spinal cord neuromodulation has emerged as a leading intervention for restoring autonomic functions, such as blood pressure, lower urinary tract (LUT), bowel, and sexual functions, following spinal cord injury (SCI). While a few preliminary studies have shown the potential effect of non-invasive transcutaneous spinal cord stimulation (tSCS) on autonomic recovery following SCI, the optimal stimulation parameters, as well as real-time and long-term functional benefits of tSCS are understudied. This trial entitled "Non-invasive Neuromodulation to Treat Bladder, Bowel, and Sexual Dysfunction following Spinal Cord Injury" is a pilot trial to examine the feasibility, dosage effect and safety of tSCS on pelvic organ function for future large-scale randomized controlled trials. METHODS AND ANALYSIS: Forty eligible participants with chronic cervical or upper thoracic motor-complete SCI will undergo stimulation mapping and assessment batteries to determine the real-time effect of tSCS on autonomic functions. Thereafter, participants will be randomly assigned to either moderate or intensive tSCS groups to test the dosage effect of long-term stimulation on autonomic parameters. Participants in each group will receive 60 minutes of tSCS per session either twice (moderate) or five (intensive) times per week, over a period of six weeks. Outcome measures include: (a) changes in bladder capacity through urodynamic studies during real-time and after long-term tSCS, and (b) resting anorectal pressure determined via anorectal manometry during real-time tSCS. We also measure assessments of sexual function, neurological impairments, and health-related quality of life using validated questionnaires and semi-structured interviews. ETHICS AND DISSEMINATION: Ethical approval has been obtained (CREB H20-01163). All primary and secondary outcome data will be submitted to peer-reviewed journals and disseminated among the broader scientific community and stakeholders.

May I Have This Dance: A Case-Series on the Acute Cardiometabolic Demand of Wheelchair Dancing in Recreational Dancers with Spinal Cord Injury.

OBJECTIVES: This case-series investigated energy expenditure, cardiovascular responses, and psychosocial outcomes during two wheelchair dancing routines with different tempos. METHODS: Three individuals with chronic, non-traumatic spinal cord injuries [males, mean age 42 (13) years, C3-T12, AIS D, schwannoma=1, poliomyelitis=1, ependymoma=1] performed slow (rumba, 80 bpm) and fast (salsa, 170 bpm) wheelchair dance routines. Physiological [heart rate, blood pressure, relative oxygen consumption (VO2), metabolic task equivalent] and psychosocial parameters [ratings of perceived exertion, enjoyment and Brunel Mood Score] were measured pre, during, and post-dancing. RESULTS: All participants showed an elevation in heart rate and relative VO2 from rest to dancing with a subsequent decrease in these parameters post-dance for both routines. Relative to the slow dance routine, two out of three participants demonstrated greater heart rate, relative VO2, ratings of perceived exertion, and enjoyment during the fast dance routine. For all three participants, metabolic task equivalents ranged from 1.7-2.4 (slow) and 2.1-3.8 (fast), suggesting the intervention was of light to moderate intensity for slow and fast dance routines, respectively. Enjoyment ratings ranged from "quite a bit" to "extremely." No differences in Brunel mood subscales were observed. CONCLUSION: This case-series offers a preliminary understanding of the acute cardiometabolic and psychosocial responses to wheelchair dance routines of differing intensities per¬formed by individuals with spinal cord injury. Responsiveness observed among these participants suggests the potential use of wheelchair dance for promoting physical activity and improving psychological well-being.

When the whole is greater than the sum of its parts: a scoping review of activity-based therapy paired with spinal cord stimulation following spinal cord injury.

Spinal cord injury (SCI) results in both motor and autonomic impairments, which can negatively affect independence and quality of life and increase morbidity and mortality. Despite emerging evidence supporting the benefits of activity-based training and spinal cord stimulation as two distinct interventions for sensorimotor and autonomic recovery, the combined effects of these modalities are currently uncertain. This scoping review evaluated the effectiveness of paired interventions (exercise + spinal neuromodulation) for improving sensorimotor and autonomic functions in individuals with SCI. Four electronic databases were searched for peer-reviewed manuscripts (Medline, Embase, CINAHL, and EI-compedex Engineering Village) and data were independently extracted by two reviewers using pre-established extraction tables. A total of 15 studies representing 79 participants were included in the review, of which 73% were conducted within the past 5 years. Only two of the studies were randomized controlled studies, while the other 13 studies were case or case-series designs. Compared with activity-based training alone, spinal cord stimulation combined with activity-based training improved walking and voluntary muscle activation, and augmented improvements in lower urinary tract, bowel, resting metabolic rate, peak oxygen consumption, and thermoregulatory function. Spinal neuromodulation in combination with use-dependent therapies may provide greater neurorecovery and induce long-term benefits for both motor and autonomic function beyond the capacity of traditional activity-based therapies. However, evidence for combinational approaches is limited and there is no consensus for outcome measures or optimal protocol parameters, including stimulation settings. Future large-scale randomized trials into paired interventions are warranted to further investigate these preliminary findings.

"I was like intoxicated with this positivity": the politics of hope amongst participants in a trial of a novel spinal cord injury rehabilitation technology in South Africa.

PURPOSE: This study discussed the reports by participants in a randomised controlled trial of a novel intervention for spinal cord injury (SCI) rehabilitation in Cape Town, South Africa. MATERIALS AND METHODS: Sixteen participants were randomised to rehabilitation involving the use of robotic locomotor training, a novel technology, or to a group receiving an activity-based intervention. All participants were interviewed before the intervention and at six months follow-up. RESULTS: In a context in which rehabilitation services for SCI are virtually non-existent, all participants approached the study with enthusiasm and expressed gratitude for participation. They had high hopes for what the programme could achieve, with many believing, perhaps incorrectly, that the programme would help them walk independently again. While hope and enthusiasm are useful for adherence to experimental intervention studies, there is a danger, especially in poorly resourced contexts, for participants to experience considerable disappointment following false hope not being realised. This raises important ethical issues for researchers interested in the potential of new technologies to promote health in poorly resourced contexts. CONCLUSIONS: For clinicians, the path between supporting positive emotions (which may lead to positive outcomes), and confronting unrealistic hope (which may lead to negative outcomes) may be difficult. Follow-up with participants after re-integration into their communities is important to determine long-term psychological impact.Pan African Clinical Trial Number: PACTR201608001647143IMPLICATIONS FOR REHABILITATIONIn low-resource contexts where there is a low level of access to rehabilitation services, such access in the context of a trial of a new intervention may engender hope in a group of people with spinal cord injury. This hope may increase when a new technology is used, as was the case in this study.Hope can be very helpful to people entering rehabilitation, but unrealistic hope and expectations may have negative implications in the longer term.In this study, expectations of participants centred, unrealistically, around regaining the ability to walk again, despite past experiences and medical advice suggesting otherwise.A thin line exists between supporting high expectations and confronting unrealistic hope. This conundrum is difficult for the clinician, as both inappropriate hope and undue pessimism about an intervention have the potential to cause harm.Participant follow-up after the end of any innovative trial is important, not just to monitor physical progress, but also, where necessary, to support participants through a potential period of disillusionment when they find their expectations have not been fully met.

Robotic Walking to Mitigate Bone Mineral Density Decline and Adverse Body Composition in Individuals With Incomplete Spinal Cord Injury: A Pilot Randomized Clinical Trial.

OBJECTIVE: The aim of the study was to determine whether 24 wks of robotic locomotor training or activity-based training was sufficient time to induce bone mineral density and body composition changes in individuals with spinal cord injury. This study reports the secondary analysis of a randomized pilot trial. DESIGN: Participants with chronic motor incomplete tetraplegia ( N = 16) were recruited. Interventions involved 60-min sessions, 3× per week, over 24 wks. Robotic locomotor training involved walking in the Ekso GT suit. Activity-based training involved a combination of resistance, cardiovascular, and weight-bearing exercise. RESULTS: Hip bone mineral density was maintained during robotic locomotor training; however, it was significantly reduced ( P = 0.04, effect size = 0.86) during activity-based training by 0.03 (-0.29 to 0.23) g/cm 2 after intervention. Both interventions improved arm fat-free soft tissue mass, but neither group experienced changes in leg fat-free soft tissue mass. The activity-based training group had a significant decrease in visceral adipose tissue ( P = 0.04, effect size = 0.72) and gynoid fat mass ( P = 0.01, effect size = 0.62). CONCLUSIONS: Twenty-four weeks of robotic locomotor training is possibly a sufficient duration to prevent the progressive decline of bone mineral density usually occurring in this population. A longitudinal period of activity-based training serves as an effective rehabilitation strategy to reduce indices of fat mass in individuals with spinal cord injury.

Robotic Locomotor Training Leads to Cardiovascular Changes in Individuals With Incomplete Spinal Cord Injury Over a 24-Week Rehabilitation Period: A Randomized Controlled Pilot Study.

OBJECTIVE: To describe the effect of robotic locomotor training (RLT) and activity-based training (ABT) on cardiovascular indices during various physiological positions in individuals with spinal cord injury. DESIGN: Randomized controlled pilot study. SETTING: Private practice: Therapy & Beyond Centre - Walking with Brandon Foundation, Sports Science Institute of South Africa, Cape Town, South Africa. PARTICIPANTS: Participants with chronic traumatic motor incomplete tetraplegia (N=16) who resided in the Western Cape, South Africa. INTERVENTION: Robotic locomotor training (Ekso GT) and activity-based training over a 24-week intervention. MAIN OUTCOME MEASURES: Brachial and ankle blood pressure, heart rate, heart rate variability, and cardiovascular efficiency during 4 physiological positions. RESULTS: No differences between groups or over time were evident in resting systolic and diastolic blood pressure, ankle systolic pressure, ankle brachial pressure index, and heart rate variability. Standing heart rate at 24 weeks was significantly higher in the ABT group (95.58±12.61 beats/min) compared with the RLT group (75.14±14.96 beats/min) (P=.05). In the RLT group, no significant changes in heart rate variability (standard deviation R-R interval and root mean square of successive differences) was found between the standing and 6-minute walk test physiological positions throughout the intervention. Cardiovascular efficiency in the RLT group during the 6-minute walk test improved from 11.1±2.6 at baseline to 7.5±2.8 beats per meter walked at 6 weeks and was maintained from 6 to 24 weeks. CONCLUSIONS: Large effect sizes and significant differences between groups found in this pilot study support the clinical effectiveness of RLT and ABT for changing cardiovascular indices as early as 6 weeks and up to 24 weeks of rehabilitation. RLT may be more effective than ABT in improving cardiac responses to orthostatic stress. Based on heart rate variability metrics, the stimulus of standing has comparable effects to RLT on the parasympathetic nervous system. Cardiovascular efficiency of exoskeleton walking improved, particularly over the first 6 weeks. Both the RLT and ABT interventions were limited in their effect on brachial and ankle blood pressure. A randomized controlled trial with a larger sample size is warranted to further examine these findings.

Effectiveness of over-ground robotic locomotor training in improving walking performance, cardiovascular demands, secondary complications and user-satisfaction in individuals with spinal cord injuries: A systematic review.

OBJECTIVES: To evaluate the effectiveness of over-ground robotic locomotor training in individuals with spinal cord injuries with regard to walking performance, cardiovascular demands, secondary health complications and user-satisfaction. DATA SOURCES: PubMed, Cochrane, Web of Science, Scopus, EBSCOhost and Engineering Village. STUDY SELECTION: Trials in which robotic locomotor training was used for a minimum of 3 participants with spinal cord injury. DATA EXTRACTION: Independent extraction of data by 2 reviewers using a pre-established data abstraction table. Quality of evidence assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). DATA SYNTHESIS: Total of 27 non-controlled studies representing 308 participants. Most studies showed decreases in exertion ratings, pain and spasticity and reported positive well-being post-intervention. Seven studies were included in meta-analyses on walking performance, showing significant improvements post-intervention (p < 0.05), with pooled effects for the 6-min walking test and 10-metre walking test of-0.94 (95% confidence interval (95% CI) -1.53,-0.36) and -1.22 (95% CI -1.87,-0.57), respectively. The Timed Up and Go Test showed a positive pooled effect of 0.74 (95% CI 0.36, 1.11). Improvements in walking parameters were seen with an increase in session number; however, no significant cardiovascular changes were found over time. CONCLUSION: Robotic locomotor training shows promise as a tool for improving neurological rehabilitation; however, there is limited evidence regarding its training benefits. Further high-powered, randomized controlled trials, with homogenous samples, are required to investigate these effects.

Bronchodilator responsiveness in children with asthma is not influenced by spacer device selection.

INTRODUCTION: Spacer devices optimize delivery of aerosol therapies and maximize therapeutic efficacy. We assessed the impact of spacer device on the prevalence and magnitude of bronchodilator response (BDR) in children with asthma. METHODS: Children with physician confirmed asthma and parentally reported symptoms in the last 12 months were recruited for this study. Each participant completed two separate visits (5-10 days apart) with spirometry performed at baseline and following cumulative doses of salbutamol (200, 400, 800, and 200 µg) delivered by either a small volume disposable spacer or a large volume multi-use spacer. Spacer type was alternated for each participant during each visit. The primary outcome was the effect of spacer type on bronchodilator responsiveness. The secondary outcome was to assess the relationships between spacer device, salbutamol dose and the proportion of children with a clinically relevant BDR. RESULTS: Thirty-two children (mean age 11.8 years) completed both visits. Change in lung function following bronchodilators was increased using the large volume spacer, for relative but not absolute increase in FEV1 [mean difference (95% confidence intervals): 1.28% (0.02, 2.54; P = 0.047) and 0.013 L (-0.01, 0.04; P = 0.288)], respectively. There was no observed difference in FVC by spacer type. Overall, 59% (n = 19) of children exhibited a clinically relevant BDR at 400 µg of salbutamol for any spacer and was independent of spacer type. CONCLUSION: Spacer device was not associated with clinically important differences in lung function following bronchodilator inhalation in children with asthma. At a recommended dose of 400 µg, some children with asthma may have their bronchodilator responsiveness misclassified.