Daily acute intermittent hypoxia to improve walking function in persons with subacute spinal cord injury: a randomized clinical trial study protocol.
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SUBMITTER: Naidu A
PROVIDER: S-EPMC7341658 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
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Daily acute intermittent hypoxia to improve walking function in persons with subacute spinal cord injury: a randomized clinical trial study protocol.
Naidu Avantika A Peters Denise M DM Tan Andrew Q AQ Barth Stella S Crane Andrea A Link Angela A Balakrishnan Swapna S Hayes Heather B HB Slocum Chloe C Zafonte Ross D RD Trumbower Randy D RD
BMC neurology 20200708 1
<h4>Background</h4>Restoring community walking remains a highly valued goal for persons recovering from traumatic incomplete spinal cord injury (SCI). Recently, studies report that brief episodes of low-oxygen breathing (acute intermittent hypoxia, AIH) may serve as an effective plasticity-inducing primer that enhances the effects of walking therapy in persons with chronic (> 1 year) SCI. More persistent walking recovery may occur following repetitive (weeks) AIH treatment involving persons with ...[more]
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Project description:ObjectivesTo test the hypothesis that daily acute intermittent hypoxia (dAIH) and dAIH combined with overground walking improve walking speed and endurance in persons with chronic incomplete spinal cord injury (iSCI).MethodsNineteen subjects completed the randomized, double-blind, placebo-controlled, crossover study. Participants received 15, 90-second hypoxic exposures (dAIH, fraction of inspired oxygen [Fio2] = 0.09) or daily normoxia (dSHAM, Fio2 = 0.21) at 60-second normoxic intervals on 5 consecutive days; dAIH was given alone or combined with 30 minutes of overground walking 1 hour later. Walking speed and endurance were quantified using 10-Meter and 6-Minute Walk Tests. The trial is registered at ClinicalTrials.gov (NCT01272349).ResultsdAIH improved walking speed and endurance. Ten-Meter Walk time improved with dAIH vs dSHAM after 1 day (mean difference [MD] 3.8 seconds, 95% confidence interval [CI] 1.1-6.5 seconds, p = 0.006) and 2 weeks (MD 3.8 seconds, 95% CI 0.9-6.7 seconds, p = 0.010). Six-Minute Walk distance increased with combined dAIH + walking vs dSHAM + walking after 5 days (MD 94.4 m, 95% CI 17.5-171.3 m, p = 0.017) and 1-week follow-up (MD 97.0 m, 95% CI 20.1-173.9 m, p = 0.014). dAIH + walking increased walking distance more than dAIH after 1 day (MD 67.7 m, 95% CI 1.3-134.1 m, p = 0.046), 5 days (MD 107.0 m, 95% CI 40.6-173.4 m, p = 0.002), and 1-week follow-up (MD 136.0 m, 95% CI 65.3-206.6 m, p < 0.001).ConclusionsdAIH ± walking improved walking speed and distance in persons with chronic iSCI. The impact of dAIH is enhanced by combination with walking, demonstrating that combinatorial therapies may promote greater functional benefits in persons with iSCI.Classification of evidenceThis study provides Class I evidence that transient hypoxia (through measured breathing treatments), along with overground walking training, improves walking speed and endurance after iSCI.
| S-EPMC3897437 | biostudies-literature
Project description:Locomotor training (LT) is intended to improve walking function and can also reduce spasticity in motor-incomplete spinal cord injury (MISCI). Transcutaneous spinal stimulation (TSS) also influences these outcomes. We assessed feasibility and preliminary efficacy of combined LT + TSS during inpatient rehabilitation in a randomized, sham-controlled, pragmatic study. Eighteen individuals with subacute MISCI (2-6 months post-SCI) were enrolled and randomly assigned to the LT + TSS or the LT + TSSsham intervention group. Participants completed a 4-week program consisting of a 2-week wash-in period (LT only) then a 2-week intervention period (LT + TSS or LT + TSSsham). Before and after each 2-week period, walking (10 m walk test, 2-min walk test, step length asymmetry) and spasticity (pendulum test, clonus drop test, modified spinal cord injury-spasticity evaluation tool) were assessed. Sixteen participants completed the study. Both groups improved in walking speed and distance. While there were no significant between-groups differences, the LT + TSS group had significant improvements in walking outcomes following the intervention period; conversely, improvements in the LT + TSSsham group were not significant. Neither group had significant changes in spasticity, and the large amount of variability in spasticity may have obscured ability to observe change in these measures. TSS is a feasible adjunct to LT in the subacute stage of SCI and may have potential to augment training-related improvements in walking outcomes.
| S-EPMC7999894 | biostudies-literature
Project description:Abstract Despite clinical strides in the treatment of osteoporosis in several diverse medical conditions, the ability to maintain bone has proven to be exceedingly difficult in individuals with severe immobilization. Fifty to 60% of bone mineral density (BMD) at the epiphyseal and metaphyseal regions of the long-bones of the lower extremities may be lost over the first couple of years after spinal cord injury (SCI). Once a large amount of bone has been lost, it would be challenging to restore BMD, trabecular architectural integrity, and mechanical strength to provide protection against long-bone fractures of the lower extremities. Persons with neurologically complete forms of SCI have marked loss of BMD of the lower extremities, predisposing to fracture, especially at the knee. Denosumab, a commercially available human monoclonal antibody of the IgG2 immunoglobulin isotype with a high affinity and specificity for binding RANKL to antagonize its action, may provide an immunopharmacological solution to the rapid progressive deterioration of sublesional bone after SCI. Twenty-six patients with motor-complete SCI [International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) grade A and B] were randomized to receive denosumab or placebo at baseline (BL), 6, and 12 months. Ten participants in the denosumab group and 8 participants in the placebo group completed the 18-month clinical trial [ClinicalTrials.gov (NCT01983475)]. Dual energy x-ray absorptiometry (DXA; Lunar Prodigy Advance, all software version 12.20.023; EnCORE, GE Medical Systems, Madison, WI) and peripheral quantitative computed tomography (pQCT; Stratec XCT 3000; STIM designs, Carmel, CA) imaging were performed. Within group paired analysis revealed a significant decrease for areal BMD (aBMD) from BL in the placebo group that started at month 3 for the distal femoral epiphysis (DFE), distal femoral metaphysis (DFM), and total hip (TH) and at month 6 for the femoral neck (FN), and at month 12 for the proximal tibial epiphysis (PTE); the loss in aBMD progressed to 18 months for all the skeletal regions of interest (ROI). At 18 months, the percent change at the ROI for the denosumab vs. placebo groups were: DFE (1.1% ± 7.5 vs. -30.0% ± 11.9, respectively, p<0.001 and p<0.001), DFM (1.2% ± 6.4 vs. -17.2% ± 14.2, p<0.01), TH (3.3% ± 8.7 vs. -25.6% ± 7.6, p < 0.001), and PTE (-1.7% ± 8.2 vs. -24.1% ± 12.3, p<0.001). At 18 months, pQCT at the 4% tibial region confirmed the DXA findings at proximal tibial; at the 38% tibial region, a trend toward loss of total volumetric BMD (vBMD) was observed (-0.7% ± 4.5 vs. -16.9% ± 20.0, p<0.09), but cortical vBMD was similar between the denosumab and placebo groups, suggesting trabecular loss at the tibial shaft. In summary, the findings suggest that denosumab, if treatment is initiated within 3 months of acute SCI, appears to be an efficacious approach to maintain BMD at the knee and hip regions.
| S-EPMC7208425 | biostudies-literature
Project description:Persons with incomplete spinal cord injury (iSCI) face ongoing struggles with walking, including reduced speed and increased reliance on assistive devices (ADs). The forces underlying body weight support and gait, as measured by ground reaction forces (GRFs), are likely altered after iSCI because of weakness and AD dependence but have not been studied. The purpose of this study was to examine GRF production during overground walking after iSCI, because greater insight into GRF constraints is important for refining therapeutic interventions. Because of reduced and discoordinated motor output after iSCI, we hypothesized that persons with iSCI would exert smaller GRFs and altered GRF modifications to increased cadence compared with able-bodied (AB) persons, especially when using an AD. Fifteen persons with chronic iSCI, stratified into no AD (n = 7) and AD (n = 8) groups, walked across an instrumented walkway at self-selected and fast (115% self-selected) cadences. Fifteen age-matched AB controls walked at their own cadences and iSCI-matched conditions (cadence and AD). Results showed fore-aft GRFs are reduced in persons with iSCI compared with AB controls, with reductions greatest in persons dependent on an AD. When controlling for cadence and AD, propulsive forces were still lower in persons with iSCI. Compared with AB controls, persons with iSCI demonstrated altered GRF modifications to increased cadence. Persons with iSCI exhibit different stance-phase forces compared with AB controls, which are impacted further by AD use and slower walking speed. Minimizing AD use and/or providing propulsive biofeedback during walking could enhance GRF production after iSCI.
| S-EPMC5793954 | biostudies-literature
Project description:Study designProspective, observational study.ObjectiveTo explore the effects of exoskeletal-assisted walking (EAW) on bowel function in persons with spinal cord injury (SCI).SettingAmbulatory research facility located in a tertiary care hospital.MethodsIndividuals 18-65 years of age, with thoracic vertebrae one (T1) to T11 motor-complete paraplegia of at least 12 months duration were enrolled. Pre- and post-EAW training, participants were asked to report on various aspects of their bowel function as well as on their overall quality of life (QOL) as related to their bowel function.ResultsTen participants completed 25-63 sessions of EAW over a period of 12-14 weeks, one participant was lost to follow up due to early withdrawal after ten sessions. Due to the small sample size, each participant's results were presented descriptively in a case series format. At least 5/10 participants reported improvements with frequency of bowel evacuations, less time spent on bowel management per bowel day, fewer bowel accidents per month, reduced laxative and/or stool softener use, and improved overall satisfaction with their bowel program post-EAW training. Furthermore, 8/10 reported improved stool consistency and 7/10 reported improved bowel function related QOL. One participant reported worsening of bowel function post-EAW.ConclusionBetween 50 and 80% of the participants studied reported improvements in bowel function and/or management post-EAW training. EAW training appeared to mitigate SCI-related bowel dysfunction and the potential benefits of EAW on bowel function after SCI is worthy or further study.
| S-EPMC7145720 | biostudies-literature
Project description:Modest recovery of somatic function after incomplete spinal cord injury (SCI) has been widely demonstrated. Recently we have shown that spontaneous recovery of baroreflex regulation of sympathetic activity also occurs in rats. Dietary restriction in the form of every other day fasting (EODF) has been shown to have beneficial effects on the recovery of motor function after SCI in rats. The goal of this study was to determine if EODF augments the improvement of baroreflex regulation of sympathetic activity after chronic left thoracic (T8) surgical spinal hemisection. To determine this, we performed baroreflex tests on ad-lib fed or EODF rats 1 week or 7 weeks after left T8 spinal hemisection. One week after T8 left hemisection baroreflex testing revealed that gain of baroreflex responsiveness, as well as the ability to increase renal sympathetic nerve activity (RSNA) at low arterial pressure, was significantly impaired in the ad-lib fed but not the EODF rats compared with sham lesioned control rats. However, baroreflex tests performed 7 weeks after T8 left hemisection revealed the inability of both ad-lib and EODF rats to decrease RSNA at elevated arterial pressures. While there is evidence to suggest that EODF has beneficial effects on the recovery of motor function in rats, EODF did not significantly improve the recovery of baroreflex regulation of sympathetic activity.
| S-EPMC7387690 | biostudies-literature
Project description:Study designSingle-subject design, standard training ("B") compared with Robotic training ("C").ObjectivesTo explore the impact of robotic training on upper limb function, activities of daily living (ADL) and training experience in subacute tetraplegic inpatients.SettingInpatient subacute Norwegian spinal cord injury (SCI) unit.MethodsFour participants (C4-7, AIS A-C) completed 11 sessions of robotic training using a passive robotic exoskeleton (Armeo Spring®). Descriptive statistics and visual analyses were used for comparing standard occupational therapy and robotic training. Outcome measures included the Spinal Cord Independence Measure (SCIM-III), the Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP), and a questionnaire.ResultsAll of the participants exhibited an increase in assessments of upper limb function (GRASSP-total) right side (0.4%-61.2%), and all except for one participant (-8%) showed an increase on their left side (20.9%-106.2%). Three out of four participants had improvements in ADL function SCIM-III (ranging from 5.6% to 46.7%). Results demonstrated improvements during the robotic intervention period in five out of 28 measurements. The participants enjoyed the exercise, and found it motivating and relevant to their injury (median ranged from 3.5 to 6.5 on a 0-7 scale).ConclusionsThree out of four participants improved upper limb function and ADL independence, but the study could not confirm that improvements were due to the robotic intervention. The participants enjoyed the robotic training and found it relevant to their injury.
| S-EPMC6462035 | biostudies-literature
Project description:Spinal cord injury (SCI) results in long-term neurological and systemic consequences, including antibody-mediated autoimmunity, which has been related to impaired functional recovery. Here we show that autoantibodies that increase at the subacute phase of human SCI, 1 month after lesion, are already present in healthy subjects and directed against non-native proteins rarely present in the normal spinal cord. The increase of these autoantibodies is a fast phenomenon-their levels are already elevated before 5 days after lesion-characteristic of secondary immune responses, further supporting their origin as natural antibodies. By proteomics studies we have identified that the increased autoantibodies are directed against 16 different nervous system and systemic self-antigens related to changes known to occur after SCI, including alterations in neural cell cytoskeleton, metabolism and bone remodeling. Overall, in the context of previous studies, our results offer an explanation to why autoimmunity develops after SCI and identify novel targets involved in SCI pathology that warrant further investigation.
| S-EPMC6193075 | biostudies-literature
Project description:Spinal cord injury (SCI) results in an array of cardiometabolic complications, with obesity being the most common component risk of cardiometabolic disease (CMD) in this population. Recent Consortium for Spinal Cord Medicine Clinical Practice Guidelines for CMD in SCI recommend physical exercise as a primary treatment strategy for the management of CMD in SCI. However, the high prevalence of obesity in SCI and the pleiotropic nature of this body habitus warrant strategies for tailoring exercise to specifically target obesity. In general, exercise for obesity management should aim primarily to induce a negative energy balance and secondarily to increase the use of fat as a fuel source. In persons with SCI, reductions in the muscle mass that can be recruited during activity limit the capacity for exercise to induce a calorie deficit. Furthermore, the available musculature exhibits a decreased oxidative capacity, limiting the utilization of fat during exercise. These constraints must be considered when designing exercise interventions for obesity management in SCI. Certain forms of exercise have a greater therapeutic potential in this population partly due to impacts on metabolism during recovery from exercise and at rest. In this article, we propose that exercise for obesity in SCI should target large muscle groups and aim to induce hypertrophy to increase total energy expenditure response to training. Furthermore, although carbohydrate reliance will be high during activity, certain forms of exercise might induce meaningful postexercise shifts in the use of fat as a fuel. General activity in this population is important for many components of health, but low energy cost of daily activities and limitations in upper body volitional exercise mean that exercise interventions targeting utilization and hypertrophy of large muscle groups will likely be required for obesity management.
| S-EPMC7983638 | biostudies-literature
Project description:Individuals with spinal cord injury (SCI) often use a wheelchair for mobility due to paralysis. Powered exoskeletal-assisted walking (EAW) provides a modality for walking overground with crutches. Little is known about the EAW velocities and level of assistance (LOA) needed for these devices.The primary aim was to evaluate EAW velocity, number of sessions, and LOA and the relationships among them. The secondary aims were to report on safety and the qualitative analysis of gait and posture during EAW in a hospital setting.Twelve individuals with SCI ? 1.5 years who were wheelchair users participated. They wore a powered exoskeleton (ReWalk; ReWalk Robotics, Inc., Marlborough, MA) with Lofstrand crutches to complete 10-meter (10 MWT) and 6-minute (6MWT) walk tests. LOA was defined as modified independence (MI), supervision (S), minimal assistance (Min), and moderate assistance (Mod). Best effort EAW velocity, LOA, and observational gait analysis were recorded.Seven of 12 participants ambulated ? 0.40 m/s. Five participants walked with MI, 3 with S, 3 with Min, and 1 with Mod. Significant inverse relationships were noted between LOA and EAW velocity for both 6 MWT (Z value = 2.63, Rho = 0.79, P = .0086) and 10 MWT (Z value = 2.62, Rho = 0.79, P = .0088). There were 13 episodes of mild skin abrasions. MI and S groups ambulated with 2-point alternating crutch pattern, whereas the Min and Mod groups favored 3-point crutch gait.Seven of 12 individuals studied were able to ambulate at EAW velocities ? 0.40 m/s, which is a velocity that may be conducive to outdoor activity-related community ambulation. The ReWalk is a safe device for in-hospital ambulation.
| S-EPMC4568091 | biostudies-literature