Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial.

Intrathecal delivery of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (AD-MSC) could be utilized to treat traumatic spinal cord injury (SCI). This Phase I trial (ClinicalTrials.gov: NCT03308565) included 10 patients with American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The study's primary outcome was the safety profile, as captured by the nature and frequency of adverse events. Secondary outcomes included changes in sensory and motor scores, imaging, cerebrospinal fluid markers, and somatosensory evoked potentials. The manufacturing and delivery of the regimen were successful for all patients. The most commonly reported adverse events were headache and musculoskeletal pain, observed in 8 patients. No serious AEs were observed. At final follow-up, seven patients demonstrated improvement in AIS grade from the time of injection. In conclusion, the study met the primary endpoint, demonstrating that AD-MSC harvesting and administration were well-tolerated in patients with traumatic SCI.

Intervention Design of High-Intensity Interval Training in Individuals With Spinal Cord Injury: Narrative Review and Future Perspectives.

Background: Individuals with spinal cord injury (SCI) have lower levels of physical activity compared to the nondisabled population. Exercise guidelines recommend moderate or vigorous exercise to improve cardiovascular health and reduce cardiometabolic risk factors in persons with SCI. High-intensity interval training (HIIT) is a popular exercise choice and encompasses brief periods of vigorous exercise paired with intermittent periods of recovery. Objectives: This review describes the available literature on HIIT for individuals with SCI, including differences in protocol design and suggested areas of further investigation. Methods: Our institution's library system performed the comprehensive search. The primary keywords and phrases used to search included spinal cord injury, high-intensity interval training, tetraplegia, paraplegia, and several other related terms. Results: Initially 62 records were screened, and 36 were deemed outside the scope of this review. Twenty-six studies published between 2001 and 2021 fulfilled the eligibility criteria and were divided among two researchers for review and analysis. All records required persons with SCI and a standardized HIIT intervention. Study design varied widely with respect to mode of exercise, prescribed intensity, duration of performance intervals, and session duration. This variability necessitates further investigation into the specifics of a HIIT prescription and the associated outcomes for persons with SCI. Conclusion: Standardization of HIIT protocols may lead to more robust conclusions regarding its effects on cardiorespiratory fitness as well as mitigation of cardiometabolic risk factors. Meta-analyses will eventually be needed on proper dosing and session parameters to improve cardiorespiratory fitness and cardiometabolic risk factors.

Inpatient rehabilitation outcomes in patients with the new diagnosis of COVID-19 tractopathy: a case series.

STUDY DESIGN: Retrospective Case Series. OBJECTIVES: Describe the inpatient rehabilitation outcomes of four patients with COVID-19 tractopathy. SETTING: Olmsted County, Minnesota, United States of America. METHODS: Retrospective review of medical records was performed to collect patient data. RESULTS: Four individuals (n = 4, 3 men and 1 woman, mean age 58.25 years [range 56-61]) completed inpatient rehabilitation during the COVID-19 pandemic. All presented after COVID-19 infection and were admitted to acute care with progressive paraparesis. None were able to ambulate on admission to acute care. All received extensive evaluations which were largely negative except for mildly elevated CSF protein and MRI findings of longitudinally extensive T2 hyperintensity signal changes in the lateral (n = 3) and dorsal (n = 1) columns. All patients experienced incomplete spastic paraparesis. All patients experienced neurogenic bowel dysfunction; a majority experienced neuropathic pain (n = 3); half experienced impaired proprioception (n = 2); and a minority experienced neurogenic bladder dysfunction (n = 1). Between rehabilitation admission and discharge, the median improvement in lower extremity motor score was 5 (0-28). All patients were discharged home, but only one was a functional ambulator at time of discharge. CONCLUSION: While the underlying mechanism is yet to be elucidated, in rare cases a COVID-19 infection can lead to a tractopathy, presenting as weakness, sensory deficits, spasticity, neuropathic pain, and neurogenic bladder/bowel. Patients with COVID-19 tractopathy would benefit from inpatient rehabilitation to enhance their functional mobility and independence.

At-Home High-Intensity Interval Training for Individuals with Paraplegia Following Spinal Cord Injury: A Pilot Study.

Objective: This pilot study aimed to assess the efficacy of a 16-week at-home high-intensity interval training (HIIT) program among individuals with spinal cord injury (SCI). Methods: Eight individuals (age: 47±11 (SD) years, 3 females) with SCI below the sixth thoracic vertebrae participated in a 16-week at-home HIIT program using an arm ergometer. Participants completed baseline graded exercise tests to determine target heart rate zones. HIIT was prescribed thrice per week. Each training session consisted of six one-minute bouts with a target heart rate ~80% heart rate reserve (HRR), interspersed with two minutes of recovery at ~30% HRR. A portable heart rate monitor and phone application provided visual feedback during training and allowed for measurements of adherence and compliance. Graded exercise tests were completed after 8 and 16 weeks of HIIT. Surveys were administered to assess participation, self-efficacy, and satisfaction. Results: Participants demonstrated a decrease in submaximal cardiac output (P=0.028) and an increase in exercise capacity (peak power output, P=0.027) following HIIT, indicative of improved exercise economy and maximal work capacity. An 87% adherence rate was achieved during the HIIT program. Participants reached a high intensity of 70% HRR or greater during ~80% of intervals. The recovery HRR target was reached during only ~35% of intervals. Self-reported metrics of satisfaction and self-efficacy with at-home HIIT scored moderate to high. Conclusion: Participants demonstrated an improvement in exercise economy and maximal work capacity following at-home HIIT. Additionally, participant adherence, compliance, satisfaction, and self-efficacy metrics suggest that at-home HIIT was easily implemented and enjoyable.

Prevalence of lateral epicondylosis in veteran manual wheelchair users participating in adaptive sports.

Objective: Determine the prevalence of lateral epicondylosis (LE) of the dominant elbow in manual wheelchair users based on ultrasound assessment and physical exam.Design: Prospective, cross-sectional.Setting: National Veteran Wheelchair Games 2018 and 2019 (event medical services).Participants: Manual wheelchair users who attended the National Veteran Wheelchair Games (n = 87).Interventions: Participants completed a questionnaire then underwent an ultrasound assessment and a physical exam of their dominant arm evaluating for common extensor tendinopathy (CET) or clinically LE.Main Outcome Measure: Prevalence of CET diagnosed by ultrasound criteria was compared with other diagnostic criteria with MaNemar test for paired binary data.Results: Forty-six percent (N = 40) of participants met diagnostic criteria for CET by ultrasound assessment and 17% (N = 15) of participants met criteria for LE based on physical exam. These values are dramatically higher than what has been reported in the able-bodied population where the prevalence is estimated to be <2%. Age and number of years of wheelchair use were significant predictors of ultrasound diagnosis of LE (P = 0.02, 95% confidence interval [CI] 1.01-1.11) and (P = 0.05, 95% CI 1.00-1.09), respectively. Association analysis based on odds ratio and CI found no association between ultrasound findings suggestive of LE with regular adaptive sport participation greater than 1.5 h per week.Conclusion: Compared to able-bodied population, there is an increased prevalence of both CET and LE in manual wheelchair users based on either ultrasound assessment or physical exam. CET is associated with increased age and increased years using a manual wheelchair. There is no association between the diagnosis of LE and participation in adaptive sport.

Biomechanical analysis of wheelchair athletes with paraplegia during cross-training exercises.

CONTEXT: Extreme conditioning programs (ECPs), such as CrossFit®, are a relatively new method of fitness with rapid growth in individuals with paraplegia. However, it is unknown if wheelchair users are at an additional risk of musculoskeletal injury during these exercises. Biomechanical characterization is necessary to determine the safety and efficacy of ECPs as an exercise modality for wheelchair users with paraplegia. OBJECTIVE: To characterize the three-dimensional (3-D) thorax and upper extremity joint kinematics of paraplegic wheelchair athletes during exercises commonly prescribed as part of ECPs. DESIGN: Observational study. PARTICIPANTS: Three male wheelchair athletes, average age of 37.1 ± 4.6 years, with spinal cord injury levels of T8, L2, and T10, with varying exercise experience. METHODS: 3-D movement was acquired using motion capture during the performance of four exercises: battle ropes, sled pull, overhead press, and sledgehammer swing. A custom upper extremity inverse kinematics model was applied to compute 3-D joint angles. OUTCOME MEASURES: 3-D peak thorax, glenohumeral, elbow, and wrist joint angles and ranges of motion (ROM), Visual Analog Scale (VAS), and Borg Scale of Perceived Exertion. RESULTS: Large joint motions were required for the exercises, at times demanding extreme shoulder and/or wrist flexion and extension, abduction, and external rotation, which are concerning for injury risk in wheelchair users. Participants, however, were able to perform the exercises pain free. CONCLUSION: These quantitative findings highlight that wheelchair athletes may be exposed to potentially injurious positions during common ECP exercises. These findings provide insight that may lead to improved clinical guidelines for prescription and training of exercise regimens, particularly involving ECPs, for wheelchair users.

Primary Melanocytomas of the Spinal Cord: Case Studies and Rehabilitation Perspectives.

Primary melanocytomas of the central nervous system are rare tumors arising from leptomeningeal melanocytes. Only 29 cases have been reported in the literature. Presenting symptoms may include insidious onset of back pain, slowly progressive neurologic deficits such as weakness and sensory changes, and bowel and bladder dysregulation. Advanced imaging including magnetic resonance imaging can be helpful in lesion localization but does not distinguish between primary and metastatic melanoma. In this case series, we present 3 patients with nontraumatic spinal cord injuries secondary to primary central nervous system malignant melanocytomas who were admitted to a single inpatient rehabilitation facility within a 12-month time frame. These cases highlight the importance of the rehabilitation team in the continuum of care for patients undergoing resection of primary melanocytomas of the spinal cord. The rehabilitation team should be involved in the preoperative counseling setting, immediately postoperatively, and in follow-up care to assess for signs of recurrence. A comprehensive multidisciplinary approach including physical and occupational therapists, rehabilitation nurses, rehabilitation neuropsychologists, and physiatrists is important for optimizing the function of these patients.

Impact of long-term epidural electrical stimulation enabled task-specific training on secondary conditions of chronic paraplegia in two humans.

Introduction: Spinal cord injury (SCI) often results in chronic secondary health conditions related to autonomic and metabolic dysfunction. Epidural electrical stimulation (EES) combined with task-specific training has been shown to enable motor function in individuals with chronic paralysis. The reported effects of EES on secondary health conditions, such as bladder function and body composition, are limited. We report the impact of EES on SCI-related secondary health changes in bladder function and body composition.Methods: Two participants with motor and sensory complete SCI performed 6 months of rehabilitation without EES followed by 12 months of task-specific training with EES after implantation of a 16-electrode array on the surface of the lumbosacral spinal cord. Participants performed three days of training per week in the laboratory, and additionally performed task-specific activities with EES at home during this time frame. Changes in bladder and body composition were recorded via clinically-available testing of neurogenic bladder functionality and dual-energy X-ray absorptiometry, respectively.Results: In one participant, we observed an increase in episodes of urinary incontinence with worsening bladder compliance and pressures at the end of the study. Bone mineral density changes were insignificant in both participants; however, one participant showed a substantial increase in lean mass (+9.1 kg; 6 months of training) via redistribution of body fat through an android/gynoid ratio reduction (-0.15; 6 months of training).Conclusion: EES optimized for standing and stepping may negatively impact neurogenic bladder functionality. Close monitoring of bladder health is imperative to prevent undesirable bladder compliance, which can lead to upper urinary tract deteriorations. Conversely, EES may serve as an adjunct tool with regular exercise modalities to improve body composition through activation of musculature innervated by spinal segments that are below the SCI.

Epidural Electrical Stimulation of the Lumbosacral Spinal Cord Improves Trunk Stability During Seated Reaching in Two Humans With Severe Thoracic Spinal Cord Injury.

Background: Quality of life measurements indicate that independent performance of activities of daily living, such as reaching to manipulate objects, is a high priority of individuals living with motor impairments due to spinal cord injury (SCI). In a small number of research participants with SCI, electrical stimulation applied to the dorsal epidural surface of the spinal cord, termed epidural spinal electrical stimulation (ES), has been shown to improve motor functions, such as standing and stepping. However, the impact of ES on seated reaching performance, as well as the approach to identifying stimulation parameters that improve reaching ability, have yet to be described. Objective: Herein, we characterize the effects of ES on seated reaching performance in two participants with chronic, complete loss of motor and sensory functions below thoracic-level SCI. Additionally, we report the effects of delivering stimulation to discrete cathode/anode locations on a 16-contact electrode array spanning the lumbosacral spinal segments on reach distance while participants were seated on a mat and/or in their wheelchair. Methods: Two males with mid-thoracic SCI due to trauma, each of which occurred more than 3 years prior to study participation, were enrolled in a clinical trial at Mayo Clinic, Rochester, MN, USA. Reaching performance was assessed, with and without ES, at several time points throughout the study using the modified functional reach test (mFRT). Altogether, participant 1 performed 1,164 reach tests over 26-time points. Participant 2 performed 480 reach tests over 17-time points. Results: Median reach distances during ES were higher for both participants compared to without ES. Forward reach distances were greater than lateral reach distances in all environments, mat or wheelchair, for both participants. Stimulation delivered in the caudal region of the array resulted in improved forward reach distance compared to stimulation in the rostral region. For both participants, when stimulation was turned off, no significant changes in reach distance were observed throughout the study. Conclusion: ES enhanced seated reaching-performance of individuals with chronic SCI. Additionally, electrode configurations delivering stimulation in caudal regions of the lumbosacral spinal segments may improve reaching ability compared to rostral regions.

Alterations of Spinal Epidural Stimulation-Enabled Stepping by Descending Intentional Motor Commands and Proprioceptive Inputs in Humans With Spinal Cord Injury.

Background: Regaining control of movement following a spinal cord injury (SCI) requires utilization and/or functional reorganization of residual descending, and likely ascending, supraspinal sensorimotor pathways, which may be facilitated via task-specific training through body weight supported treadmill (BWST) training. Recently, epidural electrical stimulation (ES) combined with task-specific training demonstrated independence of standing and stepping functions in individuals with clinically complete SCI. The restoration of these functions may be dependent upon variables such as manipulation of proprioceptive input, ES parameter adjustments, and participant intent during step training. However, the impact of each variable on the degree of independence achieved during BWST stepping remains unknown. Objective: To describe the effects of descending intentional commands and proprioceptive inputs, specifically body weight support (BWS), on lower extremity motor activity and vertical ground reaction forces (vGRF) during ES-enabled BWST stepping in humans with chronic sensorimotor complete SCI. Furthermore, we describe perceived changes in the level of assistance provided by clinicians when intent and BWS are modified. Methods: Two individuals with chronic, mid thoracic, clinically complete SCI, enrolled in an IRB and FDA (IDE G150167) approved clinical trial. A 16-contact electrode array was implanted in the epidural space between the T11-L1 vertebral regions. Lower extremity motor output and vertical ground reaction forces were obtained during clinician-assisted ES-enabled treadmill stepping with BWS. Consecutive steps were achieved during various experimentally-controlled conditions, including intentional participation and varied BWS (60% and 20%) while ES parameters remain unchanged. Results: During ES-enabled BWST stepping, the knee extensors exhibited an increase in motor activation during trials in which stepping was passive compared to active or during trials in which 60% BWS was provided compared to 20% BWS. As a result of this increased motor activation, perceived clinician assistance increased during the transition from stance to swing. Intentional participation and 20% BWS resulted in timely and purposeful activation of the lower extremities muscles, which improved independence and decreased clinician assistance. Conclusion: Maximizing participant intention and optimizing proprioceptive inputs through BWS during ES-enabled BWST stepping may facilitate greater independence during BWST stepping for individuals with clinically complete SCI. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02592668.

CELLTOP Clinical Trial: First Report From a Phase 1 Trial of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells in the Treatment of Paralysis Due to Traumatic Spinal Cord Injury.

Spinal cord injury (SCI) is a devastating condition with limited pharmacological treatment options to restore function. Regenerative approaches have recently attracted interest as an adjuvant to current standard of care. Adipose tissue-derived (AD) mesenchymal stem cells (MSCs) represent a readily accessible cell source with high proliferative capacity. The CELLTOP study, an ongoing multidisciplinary phase 1 clinical trial conducted at Mayo Clinic (ClinicalTrials.gov Identifier: NCT03308565), is investigating the safety and efficacy of intrathecal autologous AD-MSCs in patients with blunt, traumatic SCI. In this initial report, we describe the outcome of the first treated patient, a 53-year-old survivor of a surfing accident who sustained a high cervical American Spinal Injury Association Impairment Scale grade A SCI with subsequent neurologic improvement that plateaued within 6 months following injury. Although he improved to an American Spinal Injury Association grade C impairement classification, the individual continued to be wheelchair bound and severely debilitated. After study enrollment, an adipose tissue biopsy was performed and MSCs were isolated, expanded, and cryopreserved. Per protocol, the patient received an intrathecal injection of 100 million autologous AD-MSCs infused after a standard lumbar puncture at the L3-4 level 11 months after the injury. The patient tolerated the procedure well and did not experience any severe adverse events. Clinical signs of efficacy were observed at 3, 6, 12, and 18 months following the injection in both motor and sensory scores based on International Standards for Neurological Classification of Spinal Cord Injury. Thus, in this treated individual with SCI, intrathecal administration of AD-MSCs was feasible and safe and suggested meaningful signs of improved, rather than stabilized, neurologic status warranting further clinical evaluation.

Functional outcomes in patients with co-occurring traumatic brain injury and spinal cord injury from an inpatient rehabilitation facility's perspective.

Objective To examine the occurrence and severity of co-occurring traumatic brain injury (TBI) in persons with traumatic spinal cord injury (SCI), i.e. dual diagnosis (DD), and to describe differences in functional outcomes between persons with DD and SCI only from an inpatient rehabilitation facility (IRF) perspective. Design Retrospective clinical chart review. Setting Acute Midwest SCI inpatient rehabilitation facility. Participants 256 persons age 18-80 years with acute traumatic SCI (AIS A-E, C1-S3 level of injury) from 2002-2012. Interventions Neuroimaging and electronic medical records were reviewed to identify those with co-occurring TBI. Outcomes were then compared between the SCI only and DD groups. Outcome Measures Length of stay (LOS), discharge location and functional independence measures (FIM) Results Forty-one percent of persons with traumatic SCI experienced co-occurring TBI. Rehabilitation LOS for the DD groups did not differ significantly from the SCI only group. Those with Moderate-Severe DD had significantly lower Total admission FIM (P < 0.001), Cognitive admission and discharge FIM (both P < 0.001) and Motor FIM efficiency scores (P = 0.03) compared to those with SCI only and were significantly less likely to discharge home (P = 0.05). Conclusions Persons admitted to IRFs with Moderate-Severe DD compared to those with SCI only are less efficient in obtaining motor skills and may require ongoing rehabilitation to safely return home. It is therefore imperative to initiate early discharge planning and educate rehabilitation team members and families on the additional time and resources necessary to achieve more successful outcomes in those with Moderate-Severe DD.

External Iliac Artery Vasospasm in an Elite Female Runner.

A 33-year-old elite female runner presented to a tertiary care sports medicine clinic with a 2-year history of progressive anterior thigh and circumferential leg pain with associated foot paresthesias brought on by high-intensity running. She had both external iliac artery vasospasm and chronic exertional compartment syndrome. External iliac artery vasospasm is a rare cause of exertional leg pain, particularly in the running population. This case highlights the unique features of this condition, addresses the multidisciplinary approach that led to the accurate diagnoses, and demonstrates that more than 1 etiology for exertional leg pain can coexist in an athlete.

The Feasibility and Effects of Acupuncture in an Adolescent Nordic Ski Population.

BACKGROUND: Studies investigating the use and effectiveness of acupuncture in adults after exercise have been well documented. Fewer studies involving acupuncture have been completed in the adolescent athlete population. To our knowledge, there are no published studies that investigate the use of acupuncture in adolescent athletes within their field of play. OBJECTIVE: To primarily assess the feasibility of performing acupuncture in adolescent Nordic skiers within their athletic environment, and secondarily to measure the effect of acupuncture on muscle soreness and sense of well-being. DESIGN: Prospective feasibility study. SETTING: Local outdoor cross country ski trails and indoor lodge. PARTICIPANTS: Fifteen healthy participants (80% female, 20% male; age 14-17 years) were involved on at least 1 of 5 treatment days. INTERVENTION: Fifteen-minute treatments were administered using traditional needle acupuncture following the first 5 consecutive Nordic Ski Team practices of the season in an attempt to capture the effect of acupuncture on delayed-onset muscle soreness (DOMS). Acupuncture points specific to muscle groups in the lower limbs that are commonly reported as painful during Nordic skiing were chosen. Pre- and posttreatment surveys included visual analogue scales (VAS) to track participant responses. OUTCOME MEASURES: Time, cost, side effects, and participant to provider ratio was observed to determine feasibility. Effect on muscle soreness and sense of well-being was measured via pre- and posttreatment VAS (0-10) rating analyses. RESULTS: Total time required by research staff on treatment days was 90 minutes; total cost, $1500; temperature range, -13.9°C to -2.8°C, and largest participant to acupuncturist ratio, 7:1. No major side effects occurred. The majority (73%) of participants reported minimal side effects; most common was treatment site pain. The overall pre- to posttreatment effect on muscle soreness (average over 5 days) demonstrated significantly improved posttreatment scores (P = .04). The effect of the day (average over pre- and posttreatment values) demonstrated significantly higher muscle soreness scores on day 3 versus day 1 (P = .03). At study completion, all participants indicated that they would consider acupuncture in the future and would recommend treatments to friends or teammates. CONCLUSION: Providing acupuncture to adolescent Nordic ski athletes in the practice field under extreme temperatures is feasible with the appropriate resources. Despite mild side effects, acupuncture was well received by the athletes. Lessons learned from this trial can provide a framework for delivering acupuncture to other athletes in their training environment. LEVEL OF EVIDENCE: IV.

Acute visual loss in a patient with spinal cord injury.

INTRODUCTION: Patients with spinal cord injury (SCI), especially those with injury at and above T6, are prone to transient episodes of hypertension induced by noxious triggers below the level of SCI, known as autonomic dysreflexia (AD). An uncommonly reported presentation of AD is posterior reversible encephalopathy syndrome (PRES). CASE PRESENTATION: A 50-year-old male with the history of paraplegia from SCI presented with sepsis secondary to baclofen pump and urinary tract infections. On hospital day 4, he developed acute bilateral vision loss. The next morning he had a generalized-tonic-clonic seizure followed by cardiac arrest, with return of spontaneous circulation following resuscitation. Magnetic resonance imaging brain demonstrated multifocal areas of hyperintensity on T2 fluid-attenuated inversion recovery sequence, most pronounced in the occipital lobes. Systolic blood pressures (SBP) were under 180 mmHg throughout hospital stay but above his baseline (SBP 90 mmHg). PRES was diagnosed on the basis of clinical and radiologic evidence. With strict blood pressure (BP) control, there was resolution of visual abnormalities, headaches, encephalopathy, and seizures. DISCUSSION: Although PRES has been most commonly described in malignant hypertension, it can be seen in patients with normotension or moderate hypertension who have low baseline BPs, such as patients with SCI. These patients are prone to AD due to imbalanced sympathetic outflow to vasculature below the level of injury caused by noxious stimulus. This results in massive regional vasoconstriction leading to an uncontrolled rise in BP above baseline. This episode of PRES could have been prevented by identifying patient's risk, recognizing early signs and potential triggers of AD, and implementing aggressive treatment of the underlying noxious stimuli.