Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: a safety and efficacy trial.

Cervical spinal cord injury (SCI) leads to permanent impairment of arm and hand functions. Here we conducted a prospective, single-arm, multicenter, open-label, non-significant risk trial that evaluated the safety and efficacy of ARCEX Therapy to improve arm and hand functions in people with chronic SCI. ARCEX Therapy involves the delivery of externally applied electrical stimulation over the cervical spinal cord during structured rehabilitation. The primary endpoints were safety and efficacy as measured by whether the majority of participants exhibited significant improvement in both strength and functional performance in response to ARCEX Therapy compared to the end of an equivalent period of rehabilitation alone. Sixty participants completed the protocol. No serious adverse events related to ARCEX Therapy were reported, and the primary effectiveness endpoint was met. Seventy-two percent of participants demonstrated improvements greater than the minimally important difference criteria for both strength and functional domains. Secondary endpoint analysis revealed significant improvements in fingertip pinch force, hand prehension and strength, upper extremity motor and sensory abilities and self-reported increases in quality of life. These results demonstrate the safety and efficacy of ARCEX Therapy to improve hand and arm functions in people living with cervical SCI. ClinicalTrials.gov identifier: NCT04697472 .

Soluble Nogo-Receptor-Fc decoy (AXER-204) in patients with chronic cervical spinal cord injury in the USA: a first-in-human and randomised clinical trial.

BACKGROUND: Spinal cord injury (SCI) causes neural disconnection and persistent neurological deficits, so axon sprouting and plasticity might promote recovery. Soluble Nogo-Receptor-Fc decoy (AXER-204) blocks inhibitors of axon growth and promotes recovery of motor function after SCI in animals. This first-in-human and randomised trial sought to determine primarily the safety and pharmacokinetics of AXER-204 in individuals with chronic SCI, and secondarily its effect on recovery. METHODS: We conducted a two-part study in adults (aged 18-65 years) with chronic (>1 year) cervical traumatic SCI at six rehabilitation centres in the USA. In part 1, AXER-204 was delivered open label as single intrathecal doses of 3 mg, 30 mg, 90 mg, or 200 mg, with primary outcomes of safety and pharmacokinetics. Part 2 was a randomised, parallel, double-blind comparison of six intrathecal doses of 200 mg AXER-204 over 104 days versus placebo. Participants were randomly allocated (1:1) by investigators using a central electronic system, stratified in blocks of four by American Spinal Injury Association Impairment Scale grade and receipt of AXER-204 in part 1. All investigators and patients were masked to treatment allocation until at least day 169. The part 2 primary objectives were safety and pharmacokinetics, with a key secondary objective to assess change in International Standards for Neurological Classification of SCI (ISNCSCI) Upper Extremity Motor Score (UEMS) at day 169 for all enrolled participants. This trial is registered with ClinicalTrials.gov, NCT03989440, and is completed. FINDINGS: We treated 24 participants in part 1 (six per dose; 18 men, six women), and 27 participants in part 2 (13 placebo, 14 AXER-204; 23 men, four women), between June 20, 2019, and June 21, 2022. There were no deaths and no discontinuations from the study due to an adverse event in part 1 and 2. In part 2, treatment-related adverse events were of similar incidence in AXER-204 and placebo groups (ten [71%] vs nine [69%]). Headache was the most common treatment-related adverse event (five [21%] in part 1, 11 [41%] in part 2). In part 1, AXER-204 reached mean maximal CSF concentration 1 day after dosing with 200 mg of 412 000 ng/mL (SD 129 000), exceeding those concentrations that were efficacious in animal studies. In part 2, mean changes from baseline to day 169 in ISNCSCI UEMS were 1·5 (SD 3·3) for AXER-204 and 0·9 (2·3) for placebo (mean difference 0·54, 95% CI -1·48 to 2·55; p=0·59). INTERPRETATION: This study delivers the first, to our knowledge, clinical trial of a rationally designed pharmacological treatment intended to promote neural repair in chronic SCI. AXER-204 appeared safe and reached target CSF concentrations; exploratory biomarker results were consistent with target engagement and synaptic stabilisation. Post-hoc subgroup analyses suggest that future trials could investigate efficacy in patients with moderately severe SCI without prior AXER-204 exposure. FUNDING: Wings for Life Foundation, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences, National Institute on Drug Abuse, and ReNetX Bio.

Assessing functional recovery for individuals with spinal cord injury post-discharge from inpatient rehabilitation.

OBJECTIVE: To determine the associations between trauma variables, acute phase-related variables, and patient-level characteristics with functional recovery during the first-year post-discharge from inpatient rehabilitation facilities (IRF) for individuals with spinal cord injury (SCI). DESIGN: Retrospective cohort analysis. SETTING: Two SCI Model Centers in Pennsylvania, United States. METHODS: We were able to link 378 individuals with traumatic SCI between the Pennsylvania Trauma Systems Outcomes Study and the National SCI Model Systems databases. Nineteen individuals with SCI were excluded due to missing data. We estimated functional recovery based on changes in functional independence measure (FIM) total motor score during the first-year post-discharge from IRF in 359 individuals with SCI, who did not have any missing data, using ordinary least squares regression (OLS). RESULTS: After discharge from IRF the majority of individuals with SCI improved over the first-year post-injury. Individuals with cervical A-C (injury severity group) who were older had a slight decrease in motor FIM at 1-year post-injury. Regression analysis indicated that lower functional recovery was associated with being of Black and Hispanic race and ethnicity, higher injury severity group, occurrence of non-pulmonary infection during acute care, and longer length of stay at IRF (R2 = 0.36). CONCLUSIONS: Patient-level characteristics, trauma variables, and acute phase-related variables were associated with functional recovery post-discharge from IRF. Further research is necessary to collect and assess post-rehabilitation and socio-economic factors that play a critical role in continued functional recovery in the community.

Developing guiding principles for technology-based rehabilitation program by engaging people with motor incomplete tetraplegia.

BACKGROUND: Technology-aided rehabilitation is well established in the field of neurologic rehabilitation. Despite the widespread availability, the development of technology-based interventions that incorporate perspectives of the people who will use them is lacking. OBJECTIVES: This qualitative study aims to understand how people with chronic motor incomplete cervical spinal cord injury view rehabilitation technology to improve upper extremity function and neuromuscular recovery to inform future intervention development. METHODS: Seven participants with chronic upper extremity impairment due to spinal cord injury/dysfunction trialed five rehabilitation technology devices. After a 30-45 min trial for each device, participants engaged in a semi-structured interview. Interviews were analyzed using a qualitative approach to explore the experience using and understand features that support motivation to use of rehabilitation technology. RESULTS: Qualitative analysis revealed three major themes: (1) devices must be flexible to meet diverse needs; (2) intervention protocols must be individualized to address unique needs and contexts of users; (3) intervention protocols should be developed and updated by a skilled clinician. These themes and subthemes were used to describe guiding principles to inform future intervention design. CONCLUSION: The experiences of people with cervical spinal cord injury can be elicited as part of the intervention design process to systematically develop protocols for future feasibility trials. The findings from this study can be used to inform the development of technology-aided rehabilitation programs to improve upper extremity function in people with chronic motor incomplete tetraplegia. CLINICAL TRIALS REGISTRATION NUMBER: NCT04000256.

Evaluating associations between trauma-related characteristics and functional recovery in individuals with spinal cord injury.

OBJECTIVE: To determine the associations between trauma variables, acute phase-related variables, and patient-level characteristics with functional recovery during inpatient rehabilitation for individuals with spinal cord injury (SCI). The associations were evaluated by linking individuals' records between the Pennsylvania Trauma Systems Outcomes Study and the National SCI Model Systems databases. DESIGN: Retrospective cohort analysis. SETTING: Two SCI Model Centers in Pennsylvania, United States. METHODS: We used a record linkage toolkit in Python to link 735 individuals with traumatic SCI between the databases. The percentage for true-match and error were 92.0% and 0.1%, respectively. The functional recovery during inpatient rehabilitation was determined in 604 individuals with SCI by ordinary least squares regression (OLS) and gradient boosting regression (GBR) analyses. RESULTS: The OLS and GBR analyses indicated older age, greater impairment (SCI level combined with American Spinal Injury Association impairment scale), presence of diabetes mellitus, pulmonary complications during acute care, and longer length of stay at an inpatient rehabilitation facility were associated with lower functional recovery (OLS R2 = 0.56 and GBR R2 = 0.58). CONCLUSIONS: Trauma and acute care variables in addition to patient characteristics were associated with functional recovery during inpatient rehabilitation in individuals with SCI. Further investigation is needed to understand the role of diabetes mellitus and pulmonary complications, which have not been previously associated with functional recovery in individuals with SCI.

Factors associated with post-acute functional status and discharge dispositions in individuals with spinal cord injury.

BACKGROUND: Research has evaluated the effect of surgical timing on patient functional recovery in individuals with spinal cord injury (SCI); however, there is a critical need to assess how demographics, clinical characteristics, and process of care affect functional outcomes. OBJECTIVE: We examined the association between demographic, clinical, and process of care factors with post-acute functional status (locomotion and transfer mobility scores) and discharge disposition (home vs. institution) in individuals with SCI. METHODS: This study was a retrospective cohort analysis of the Pennsylvania Trauma Systems Outcomes Study (PTOS) database for individuals with traumatic SCI (N = 2223). We conducted multinomial and binomial logistic regression analyses to examine post-acute functional status and discharge disposition, respectively. RESULTS: The results indicated that older age, longer length of stay, lower Glasgow Coma Scale (GCS), higher Injury Severity Score (ISS), and individuals with tetraplegia had significantly lower motor functional score at discharge from an acute hospital. In addition, older age, individuals with public-sponsored insurance, longer length of stay, lower GCS, and higher ISS had significantly higher odds of being discharged to an institution, as compared to home. Individuals of Hispanic ethnicity, as compared to White, had lower odds of being discharged to an institution. CONCLUSIONS: The regression models developed in this study were able to better classify discharge destinations compared to the functional outcomes at discharge from the acute hospital. Further research is necessary to determine how these factors and their associations vary nationally across the US, which have the potential to inform trauma and acute care post-SCI.

Characterizing the Experience of Spasticity after Spinal Cord Injury: A National Survey Project of the Spinal Cord Injury Model Systems Centers.

OBJECTIVE: To characterize the qualities that individuals with spinal cord injury (SCI) associate with their experience of spasticity and to describe the relationship between spasticity and perceived quality of life and the perceived value of spasticity management approaches. DESIGN: Online cross-sectional survey. SETTING: Multicenter collaboration among 6 Spinal Cord Injury Model Systems hospitals in the United States. PARTICIPANTS: Individuals with SCI (N=1076). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Qualities of Spasticity Questionnaire, modified Spinal Cord Injury-Spasticity Evaluation Tool (mSCI-SET), and the modified Patient-Reported Impact of Spasticity Measure (mPRISM). RESULTS: Respondents indicated that spasms most often occurred in response to movement-related triggering events. However, spontaneous spasms (ie, no triggering event) were also reported to be among the most common types. Frequency of spasms appears to decline with age. The highest frequency of spasms was reported by 56% of respondents aged <25 years and by only 28% of those >55 years. Stiffness associated with spasticity was reported to be more common than spasms (legs, 65% vs 54%; trunk, 33% vs 18%; arms, 26% vs 15%). Respondents reported negative effects of spasticity more commonly than positive effects. Based on their association with negative scores on the mSCI-SET and the mPRISM, the 5 most problematic experiences reported were stiffness all day, interference with sleep, painful spasms, perceived link between spasticity and pain, and intensification of pain before a spasm. Respondents indicated spasticity was improved more by stretching (48%) and exercise (45%) than by antispasmodics (38%). CONCLUSIONS: The experience of spasticity after SCI is complex and multidimensional, with consequences that affect mobility, sleep, comfort, and quality of life. Stiffness, rather than spasms, appears to be the most problematic characteristic of spasticity. Physical therapeutic interventions to treat spasticity warrant in-depth investigation.

Long-Term Follow-Up of Patients With Ventilator-Dependent High Tetraplegia Managed With Diaphragmatic Pacing Systems.

OBJECTIVE: To explore participants' experiences after implantation of a diaphragmatic pacing system (DPS). DESIGN: Cross-sectional, observational study using self-report questionnaires. SETTING: Participants were recruited from 6 Spinal Cord Injury Model System centers across the United States (Craig Hospital, CO; Jefferson/Magee Rehabilitation Hospital, PA; Kessler Rehabilitation Center, NJ; University of Miami, FL; The Shirly Ryan Ability Lab, IL; Shepherd Center, GA). INTERVENTIONS: Not applicable. PARTICIPANTS: Men and women (N=28) with tetraplegia were enrolled in the study between November 2012 and January 2015. MAIN OUTCOME MEASURES: Participants completed self-report questionnaires focused on their DPS usage and mechanical ventilation, as well as their experiences and satisfaction with the DPS. RESULTS: DPS is a well-tolerated and highly successful device to help individuals living with spinal cord injury who are dependent on ventilators achieve negative pressure, ventilator-free breathing. A small percentage of participants reported complications, including broken pacing wires and surgery to replace or reposition wires. CONCLUSIONS: This study provides insight into the usage patterns of DPS and both the potential negative and positive effects that DPS can have on the life of the user. Knowledge gained from this study can provide a foundation for further discussion about the benefits and potential risks of using a DPS to inform an individual's decision to pursue a DPS implant.

Characterizing Natural Recovery of People With Initial Motor Complete Tetraplegia.

OBJECTIVE: To determine the differences in neurologic recovery in persons with initial cervical American Spinal Cord Injury Association Impairment Scale (AIS) grades A and B over time. DESIGN: Retrospective analysis of data from people with traumatic cervical spinal cord injury (SCI) enrolled in the National Spinal Cord Injury Model Systems (SCIMS) database from 2011-2019. SETTING: SCIMS centers. PARTICIPANTS: Individuals (N=187) with traumatic cervical (C1-C7 motor level) SCI admitted with initial AIS grade A and B injuries within 30 days of injury, age 16 years or older, upper extremity motor score (UEMS) ≤20 on both sides, and complete neurologic data at admission and follow-up between 6 months and 2 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Conversion in AIS grades, UEMS and lower extremity motor scores (LEMS), and sensory scores. RESULTS: Mean time to initial and follow-up examinations were 16.1±7.3 days and 377.5±93.4 days, respectively. Conversion from an initial cervical AIS grades A and B to motor incomplete status was 13.4% and 50.0%, respectively. The mean UEMS change for people with initial AIS grades A and B did not differ (7.8±6.5 and 8.8±6.1; P=.307), but people with AIS grade B experienced significantly higher means of LEMS change (2.3±7.4 and 8.8±13.9 (P≤.001). The increased rate of conversion to motor incomplete status from initial AIS grade B appears to be the primary driving factor of increased overall motor recovery. Individuals with initial AIS grade B had greater improvement in sensory scores. CONCLUSIONS: While UEMS recovery is similar in persons with initial AIS grades A and B, the rate of conversion to motor incomplete status, LEMS, and sensory recovery are significantly different. This information is important for clinical as well as research considerations.

Highlighting gaps in spinal cord injury research in activity-based interventions for the upper extremity: A scoping review.

BACKGROUND: Upper extremity activity-based therapy for neurologic disorders employs high-intensity, high repetition functional training to exploit neuroplasticity and improve function. Research focused on high-intensity upper extremity activity-based therapy for persons with spinal cord injury (SCI) is limited. OBJECTIVE: To summarize high-intensity activity-based interventions used in neurological disorders for their current or potential application to SCI. METHODS: The scoping review included articles from MEDLINE, CINAHL, Cochrane CENTRAL, and OTSeeker with the criteria: non-invasive activity-based interventions delivered at least three times/week for two weeks, upper extremity functional outcomes, age 13 years or older, English language, and neurological disorders three months post onset/injury. RESULTS: The search yielded 172 studies. There were seven studies with SCI, all in adults. Activity-based interventions in SCI included task-specific training and gaming, with and without electrical stimulation, and a robotic exoskeleton. The other populations found in the review included studies in stroke, cerebral palsy, and multiple sclerosis. Thirty-four different interventions were reported in other populations. In comparison to the extensive stroke research, work in SCI was not found for high-intensity interventions using virtual reality, brain stimulation, rehabilitation devices, and applications to the home and telerehab settings. CONCLUSION: The results highlight critical gaps within upper extremity high-intensity activity-based research in SCI.

A Comparison of Diagnostic Stability of the ASIA Impairment Scale Versus Frankel Classification Systems for Traumatic Spinal Cord Injury.

OBJECTIVE: To determine whether the "sacral sparing" definition for completeness of traumatic spinal cord injury (SCI) is a more stable definition than the previously used Frankel Classification. DESIGN: Retrospective analysis of individuals enrolled in the Spinal Cord Injury Model Systems (SCIMS) database between 2011 and 2018. SETTING: SCIMS centers. PARTICIPANTS: Individuals (N=804) with traumatic SCI who were at least 16 years old at time of injury, were admitted to rehabilitation within 30 days, had American Spinal Injury Association Impairment Scale (AIS) grades A-D at admission, and had complete neurologic data at the time of admission and 1 year. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Frankel and AIS scores were computed for a cohort of 804 eligible cases. Stability was compared between the 2 classification systems by calculating the proportions of cases in which regression (conversion to a more severe impairment level) was observed. RESULTS: A larger proportion of individuals classified with "incomplete" injuries (grades B-D) at the time of admission using the Frankel system regressed to complete status at 1 year compared with the AIS criteria (9.4% vs 2.0%). Those with grade B injuries regressed to grade A more often using the Frankel system compared with the AIS system (19.7% to 5.4%). A larger proportion of people diagnosed as Frankel grade C or D regressed to Frankel grade A compared with individuals diagnosed as AIS grade C or D who regressed to AIS grade A (5.0% to 1.1%). CONCLUSIONS: More individuals diagnosed with neurologically incomplete SCI regressed to complete status at 1 year when using the Frankel system compared with AIS classification, which is based on sacral sparing. This reinforces the finding that the "sacral sparing" definition is a more stable classification in traumatic SCI.

The effect of zoledronic acid on attenuation of bone loss at the hip and knee following acute traumatic spinal cord injury: a randomized-controlled study.

STUDY DESIGN: Randomized double blind, placebo-controlled trial. OBJECTIVES: To examine the effect of early intravenous zoledronic acid (ZA) on bone markers and areal bone mineral density (aBMD) in persons with acute ASIA Impairment Scale (AIS) A traumatic spinal cord injury (SCI). SETTING: Two inpatient rehabilitation units. METHODS: Thirteen men, 2 women, aged 19-65, C4-T10 AIS A SCI, received 5 mg intravenous ZA vs. placebo 12-21 days post injury. Markers of bone formation (procollagen N-1 terminal propeptide [P1NP]), bone resorption (serum C-telopeptide [CTX]), and aBMD by dual-energy X-ray absorptiometry (DXA) for hip (femur-proximal, intertrochanteric, neck), and knee (distal femur, proximal tibia) were obtained at baseline, 2 weeks post infusion (P1NP, CTX only), 4 and 12 months post injury. RESULTS: P1NP remained unchanged, while CTX decreased in ZA but increased in controls at 2 weeks (mean difference = -97%, p < 0.01), 4 months (mean difference = -54%, p < 0.05), but not 12 months (mean difference = 3%, p = 0.23). Changes in aBMD at the hip favored ZA at 4 months (mean difference 10.3-14.1%, p < 0.01) and 12 months (mean difference 10.8-13.1%, p < 0.02). At 4 months, changes in aBMD favored ZA at the distal femur (mean difference 6.0%, 95% CI: 0.7-11.2, p < 0.03) but not proximal tibia (mean difference 8.3%, 95% CI: -6.9 to 23.6, p < 0.23). Both groups declined in aBMD at 12 months, with no between group differences. CONCLUSION: ZA administered ≤21 days of complete traumatic SCI maintains aBMD at the hip and distal femur at 4 months post injury. This effect is partially maintained at 12 months.

Trends in Rates of ASIA Impairment Scale Conversion in Traumatic Complete Spinal Cord Injury.

Recent studies of persons with spinal cord injury (SCI) report higher conversion rates of the American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades, especially for complete injuries. We examined the rate of conversion over time after complete SCI, accounting for demographic and injury characteristics. Subjects were 16 years of age and older with a complete SCI injury between 1995 and 2015, enrolled in the National SCI Database as day-1 admissions. We grouped subjects into 3-year intervals and assessed trends in conversion for the total sample and by tetraplegia (Tetra), high paraplegia (levels T1-9, HPara), and low paraplegia (levels T10-12, LPara).We used logistic regression to identify factors related to conversion such as age, sex, etiology, and level of injury. Of 2036 subjects, 1876 subjects had a follow-up examination between 30 and 730 days post-injury. Average age at injury was 34.2 ± 14.6 years; 79.8% were male, 44.6% Tetra, 35.3% HPara, and 20.1% LPara. There was a strong trend toward increased rates of conversion over time (p < 0.01 for all groups), especially for Tetra (to incomplete from 17.6% in 1995-1997 to 50% in 2013-2015, and to motor incomplete from 9.4% to 28.1%). Conversion rates for Para were less dramatic. There were increased odds of converting to incomplete for year of injury, level of injury (Tetra >LPara >HPara), non-violent etiology, and age (older is better). We found similar factors for conversion to motor incomplete, except sex was significant and etiology was not. Conversion rates from complete to incomplete and motor incomplete injury have been increasing, particularly for persons with tetraplegia. This has implications for acute clinical trials and for prognostication early after SCI.

Reliability of S3 pressure sensation and voluntary hip adduction/toe flexion and agreement with deep anal pressure and voluntary anal contraction in classifying persons with traumatic spinal cord injury.

Context/Objective: The sacral examination components of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), namely deep anal pressure (DAP) and voluntary anal sphincter contraction (VAC), are often difficult to perform. We evaluated whether pressure sensation at the S3 dermatome (S3P), and voluntary hip adductor or toe flexor contraction (VHTC) are tenable alternatives. Here we report test-retest reliability and agreement of these components at 1 month after spinal cord injury (SCI), and impact of disagreement on American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades. Design: Longitudinal cohort. ISNCSCI examination, S3P and VHTC conducted at 1-month post-injury; retest of the sacral exam, S3P and VHTC within 3 days. Follow-up examinations performed at 3, 6, and 12 months. Setting: Five Spinal Cord Injury Model System Centers. Participants: Subjects with acute traumatic SCI, neurological levels T12 and above, AIS grades A-C. Interventions: None. Outcome Measures: ISNCSCI exam, AIS grades. Results: Fifty-one subjects had 1-month data, and 39 had at least one follow-up examination. Test-retest reliability indicated perfect agreement (kappa = 1.0) for all data except S3P (kappa = 0.96). The agreement was almost perfect between S3P and DAP (kappa = 0.84) and between VHTC and VAC (kappa = 0.81). VHTC and VAC differed more often with neurologic levels below T10, possibly due to root escape in conus medullaris injuries. Conclusion: S3P and VHTC show promise as alternatives to DAP and VAC for determining sacral sparing in persons with neurologic levels T10 and above. Reliability and agreement should be evaluated at earlier timepoints and in children with SCI.

Paralysis After Lumbar Interlaminar Epidural Steroid Injection in the Absence of Hematoma: A Case of Congestive Myelopathy Due to Spinal Dural Arteriovenous Fistula and a Review of the Literature.

Paraplegia after interlaminar epidural steroid injection is a rare event and has typically been described after epidural hematoma or direct spinal cord injury. We present a case of an 87-yr-old man who experienced transient lower limb weakness after a lumbar interlaminar epidural steroid injection due to an alternative cause, congestive myelopathy related to an underlying vascular malformation, namely, a spinal dural arteriovenous fistula. This is a poorly recognized and potentially treatable cause of progressive myelopathy. We present this case and review the literature on paraplegia after epidural steroid injection due to spinal dural arteriovenous fistula. Notably, this case of paralysis occurred in association with the lowest volume of epidural injectate reported in the literature to date (4 ml); importantly, this volume is consistent with the current clinical practice guideline standards for the safe performance of interlaminar epidural steroid injections. Physicians should be aware of this potential complication of epidural steroid injection and remain vigilant for the possibility after a procedure, even when performed according to current practice standards.

Application of Diffusion Tensor Imaging in Forecasting Neurological Injury and Recovery after Human Cervical Spinal Cord Injury.

The aim of this study is to determine the strength and accuracy of diffusion tensor imaging (DTI) parameters to predict neurological injury and recovery in adult cervical spinal cord injury (SCI). DTI magnetic resonance imaging (MRI) was performed on 23 acute cervical SCI patients within 12 h after injury and on 45 controls utilizing a rapid DTI sequence (∼5 min). Neurological assessments were conducted from within 24 h of injury up to 6 months utilizing detailed International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examinations. Spearman correlation and receiver operating characteristic (ROC) analysis were used to identify relationships between the DTI parameters at the lesion epicenter and adjacent regions, with injury severity and recovery. In proximity to the anatomical injury (within one level above and below epicenter), there was significant reduction in fractional anisotropy (FA), and elevation in mean diffusivity (MD) and radial diffusivity (RD). DTI values measured one level rostral to the injury epicenter showed stronger correlations with multiple clinical features at several time-points. Area under the curve (AUC) obtained from ROC analysis showed FA (AUC = 0.77) measured at lesion epicenter, and FA (0.83), MD (0.76), and RD (0.83) values measured immediately rostral (one level above) to epicenter discriminate injury severity. Further, MD (0.78) measured at lesion epicenter, and MD (0.79) and RD (0.74) values measured immediately rostral to epicenter discriminate neurological recovery. DTI indices measured immediately rostral to the anatomical level of injury consistently showed better correlation (moderate to strong) and accuracy in predicting neurological injury (FA, r = -0.51 and RD, r = 0.54) and recovery (MD, r = -0.51) than indices measured at the epicenter. There was weak to moderate correlation of all measures at lesion epicenter in predicting neurological injury (FA: r = -0.48; MD: r = 0.23; RD: r = 0.34; axial diffusivity [AD]: r = 0.02) and recovery (FA: r = 0.27; MD: r = -0.44; RD: r = -0.35; AD: r = -0.34).

Evaluation of the Capabilities of Upper Extremity Test (CUE-T) in Children With Tetraplegia.

Background: The Capabilities of Upper Extremity Test (CUE-T) is a spinal cord injury (SCI)-specific instrument based on the CUE Questionnaire (CUE-Q). Objective: To evaluate the psychometric properties of CUE-T in children with cervical SCI and determine the lowest age appropriate for test administration. Method: In this repeated measures multicenter study, 39 youths, mean age 12.3 years and mean time post injury 5.14 years, completed two administrations of the CUE-T. Test-retest reliability, internal consistency, and known groups validity were measured. Concurrent and discriminant validity were measured against previously validated measures: CUE-Q, Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP), Spinal Cord Independence Measure (SCIM) III, SCIM III-Self Care (SCIM-SC), and SCIM-Mobility. Results: The CUE-T scores demonstrated strong test-retest reliability (ICC ≥ 0.95), strong internal consistency (α ≥ 0.90), and acceptable individual item agreement (κ ≥ 0.49). The hand subscale had better scores (p < .05) for the motor incomplete versus complete known groups, and the arm, hand, and side subscales had better scores (p < .05) for higher versus lower strength groups. The CUE-T had strong concurrent validity with the CUE-Q (r = 0.85-0.87), GRASSP (r = 0.78-0.90), and SCIM-SC (r = 0.70) and moderate-to-weak correlation with the total SCIM (r = 0.65) and SCIM-Mobility (r = 0.51). Children older than 6 years with mature grasp patterns were able to complete the CUE-T. Conclusion: The CUE-T scores are reliable and valid for use in children with cervical SCI older than 6 years of age.

Comparison of Responsiveness and Minimal Clinically Important Difference of the Capabilities of Upper Extremity Test (CUE-T) and the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP).

Background: The Capabilities of Upper Extremity Test (CUE-T) and the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) were both developed to detect change in upper extremity (UE) function in persons with tetraplegia. Objective: To compare the responsiveness and minimal clinically important difference (MCID) of the CUE-T and the quantitative prehension (QtP) scale of the GRASSP. Methods: Subjects included 69 persons with tetraplegia: 60 with acute and 9 with chronic injuries. Subjects were assessed twice 3 months apart using the CUE-T, QtP-GRASSP, and upper extremity motor scores (UEMS). Subjects rated their impression of change in overall and right/left UE function from -7 to +7. The standardized response mean (SRM) was determined for acute subjects. MCID was estimated using a small subjective change (2-3 points) and change in UEMS. Results: Subjects were 41.9 ± 18.1 years old, neurological levels C1-C7; 25 were motor complete. For acute subjects, the SRMs for total/side CUE-T scores were 1.07/0.96, and for the QtP-GRASSP they were 0.88/0.78. MCIDs based on subjective change for total/side CUE-T scores were 11.7/6.1 points and for QtP-GRASSP were 6.4/3.0 points. Based on change in UEMS, MCIDs for total/side were 11.9/6.3 points for CUE-T and 6.0/3.3 points for QtP-GRASSP. Some subjects had changes in the CUE-T due to its arm items that were not seen with the QtP-GRASSP. Conclusion: Both the CUE-T and QtP-GRASSP are responsive to change in persons with acute cervical spinal cord injury with large SRMs. The CUE-T detects some changes in UE function not seen with the QtP-GRASSP.

Activity-based Rehabilitation Interventions of the Neurologically Impaired Upper Extremity: Description of a Scoping Review Protocol.

Introduction: A scoping review provides a means to synthesize and present a large body of literature on a broad topic, such as methods for various upper extremity activity-based therapy (ABT) interventions. Objectives: To describe our scoping review protocol to evaluate peer-reviewed articles focused on ABT interventions for individuals with neurologically impaired upper extremities. Methods: At Jefferson College of Health Professions and Sidney Kimmel Medical College at Jefferson, Philadelphia, the authors will follow this protocol to conduct a scoping review by establishing a research question and conducting a search of bibliographic databases to identify relevant studies. Using specific inclusion and exclusion criteria, abstracts will be screened and full-text articles will be reviewed for inclusion in charting, summarizing, and reporting results of appropriate studies. Conclusion: This protocol will guide the scoping review process to develop a framework for establishing a noninvasive ABT intervention informed by evidence for individuals with neurologically impaired upper extremities.

Sensitivity of the SCI-FI/AT in Individuals With Traumatic Spinal Cord Injury.

OBJECTIVE: To examine the ability of the Spinal Cord Injury-Functional Index/Assistive Technology (SCI-FI/AT) measure to detect change in persons with spinal cord injury (SCI). DESIGN: Multisite longitudinal (12-mo follow-up) study. SETTING: Nine SCI Model Systems programs. PARTICIPANTS: Adults (N=165) with SCI enrolled in the SCI Model Systems database. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: SCI-FI/AT computerized adaptive test (CAT) (Basic Mobility, Self-Care, Fine Motor Function, Wheelchair Mobility, and/or Ambulation domains) completed at discharge from rehabilitation and 12 months after SCI. For each domain, effect size estimates and 95% confidence intervals were calculated for subgroups with paraplegia and tetraplegia. RESULTS: The demographic characteristics of the sample were as follows: 46% (n=76) individuals with paraplegia, 76% (n=125) male participants, 57% (n=94) used a manual wheelchair, 38% (n=63) used a power wheelchair, 30% (n=50) were ambulatory. For individuals with paraplegia, the Basic Mobility, Self-Care, and Ambulation domains of the SCI-FI/AT detected a significantly large amount of change; in contrast, the Fine Motor Function and Wheelchair Mobility domains detected only a small amount of change. For those with tetraplegia, the Basic Mobility, Fine Motor Function, and Self-Care domains detected a small amount of change whereas the Ambulation item domain detected a medium amount of change. The Wheelchair Mobility domain for people with tetraplegia was the only SCI-FI/AT domain that did not detect significant change. CONCLUSIONS: SCI-FI/AT CAT item banks detected an increase in function from discharge to 12 months after SCI. The effect size estimates for the SCI-FI/AT CAT vary by domain and level of lesion. Findings support the use of the SCI-FI/AT CAT in the population with SCI and highlight the importance of multidimensional functional measures.