Glutathione in the Pons Is Associated With Clinical Status Improvements in Subacute Spinal Cord Injury.

OBJECTIVES: In spinal cord injury (SCI), the primary mechanical injury is followed by secondary sequelae that develop over the subsequent months and manifests in biochemical, functional, and microstructural alterations, at the site of direct injury but also in the spinal cord tissue above and below the actual lesion site. Noninvasive magnetic resonance spectroscopy (MRS) can be used to assess biochemical modulation occurring in the secondary injury phase, in addition to and supporting conventional MRI, and might help predict and improve patient outcome. In this article, we aimed to examine the metabolic levels in the pons of subacute SCI by means of in vivo proton MRS at 3 T and explore the association to clinical scores. MATERIALS AND METHODS: In this prospective study, between November 2015 and February 2018, single-voxel short-echo MRS data were acquired in healthy controls and in SCI subjects in the pons once during rehabilitation. Besides the single-point MRS examination, in addition, in participants with SCI, the clinical status (ie, motor, light touch, and pinprick scores) was assessed twice: (1) around the MRS session (approximately 10 weeks postinjury) and (2) before discharge (at approximately 9 months postinjury). The group differences were assessed with Kruskal-Wallis test, the post hoc comparison was assessed with Wilcoxon rank sum test, and the clinical correlations were conducted with Spearman rank correlation test. Bayes factor calculations completed the statistical part providing relevant evidence values. RESULTS: Twenty healthy controls (median age, 50 years; interquartile range, 41-55 years; 18 men) and 18 subjects with traumatic SCI (median age, 50 years; interquartile range, 32-58 years; 16 men) are included. Group comparison showed an increase of total N -acetylaspartate and combined glutamate and glutamine levels in complete SCI and a reduction of total creatine in incomplete paraplegic SCI. The proton MRS-based glutathione levels at baseline correlate to the motor score improvement during rehabilitation in incomplete subacute SCI. CONCLUSIONS: This exploratory study showed an association of the metabolite concentration of glutathione in the pons assessed at approximately 10 weeks after injury with the improvements of the motor score during the rehabilitation. Pontine glutathione levels in subjects with traumatic subacute incomplete SCI acquired remote from the injury site correlate to clinical score and might therefore be beneficial in the rehabilitation assessments.

Stimulation of paralysed quadriceps muscles with sequentially and spatially distributed electrodes during dynamic knee extension.

BACKGROUND: During functional electrical stimulation (FES) tasks with able-bodied (AB) participants, spatially distributed sequential stimulation (SDSS) has demonstrated substantial improvements in power output and fatigue properties compared to conventional single electrode stimulation (SES). The aim of this study was to compare the properties of SDSS and SES in participants with spinal cord injury (SCI) in a dynamic isokinetic knee extension task simulating knee movement during recumbent cycling. METHOD: Using a case-series design, m. vastus lateralis and medialis of four participants with motor and sensory complete SCI (AIS A) were stimulated for 6 min on both legs with both electrode setups. With SES, target muscles were stimulated by a pair of electrodes. In SDSS, the distal electrodes were replaced by four small electrodes giving the same overall stimulation frequency and having the same total surface area. Torque was measured during knee extension by a dynamometer at an angular velocity of 110 deg/s. Mean power of the left and right sides (PmeanL,R) was calculated from all stimulated extensions for initial, final and all extensions. Fatigue is presented as an index value with respect to initial power from 1 to 0, whereby 1 means no fatigue. RESULTS: SDSS showed higher PmeanL,R values for all four participants for all extensions (increases of 132% in participant P1, 100% in P2, 36% in P3 and 18% in P4 compared to SES) and for the initial phase (increases of 84%, 59%, 66%, and 16%, respectively). Fatigue resistance was better with SDSS for P1, P2 and P4 but worse for P3 (0.47 vs 0.35, 0.63 vs 0.49, 0.90 vs 0.82 and 0.59 vs 0.77, respectively). CONCLUSION: Consistently higher PmeanL,R was observed for all four participants for initial and overall contractions using SDSS. This supports findings from previous studies with AB participants. Fatigue properties were better in three of the four participants. The lower fatigue resistance with SDSS in one participant may be explained by a very low muscle activation level in this case. Further investigation in a larger cohort is warranted.

Multi-Day Recordings of Wearable Sensors Are Valid and Sensitive Measures of Function and Independence in Human Spinal Cord Injury.

Wearable sensor assessment tools have proven to be reliable in measuring function in normal and impaired movement disorders during well-defined assessment protocols. While such assessments can provide valid and sensitive measures of upper limb activity in spinal cord injury (SCI), no assessment tool has yet been introduced into unsupervised daily recordings to complement clinical assessments during rehabilitation. The objective of this study was to measure the overall amount of upper-limb activity in subjects with acute SCI using wearable sensors and relate this to lesion characteristics, independence, and function. The overall amount of upper extremity activity counts, measures of wheeling (speed and distance), and limb-use laterality were measured in 30 in-patients with an acute cervical or thoracic SCI three months after injury. The findings were related to the international standards for neurological classification of SCI, the spinal cord independence measure, and the upper extremity motor scores of the Graded and Redefined Assessment of Strength, Sensibility, and Prehension. Overall upper extremity activity counts were successfully recorded in all patients and correlated with the neurological level of injury and independence. Clinical measures of proximal muscle strength were related to overall activity count and peak velocity of wheeling. Compared with paraplegics, tetraplegics showed significantly lower activity counts and increased limb-use laterality. This is the first cross-sectional study showing the feasibility and clinical value of sensor recordings during unsupervised daily activities in rehabilitation. The strong relationship between sensor-based measures and clinical outcomes supports the application of such technology to assess and track changes in function during rehabilitation and in clinical trials.

Monitoring Upper Limb Recovery after Cervical Spinal Cord Injury: Insights beyond Assessment Scores.

BACKGROUND: Preclinical investigations in animal models demonstrate that enhanced upper limb (UL) activity during rehabilitation promotes motor recovery following spinal cord injury (SCI). Despite this, following SCI in humans, no commonly applied training protocols exist, and therefore, activity-based rehabilitative therapies (ABRT) vary in frequency, duration, and intensity. Quantification of UL recovery is limited to subjective questionnaires or scattered measures of muscle function and movement tasks. OBJECTIVE: To objectively measure changes in UL activity during acute SCI rehabilitation and to assess the value of wearable sensors as novel measurement tools that are complimentary to standard clinical assessments tools. METHODS: The overall amount of UL activity and kinematics of wheeling were measured longitudinally with wearable sensors in 12 thoracic and 19 cervical acute SCI patients (complete and incomplete). The measurements were performed for up to seven consecutive days, and simultaneously, SCI-specific assessments were made during rehabilitation sessions 1, 3, and 6 months after injury. Changes in UL activity and function over time were analyzed using linear mixed models. RESULTS: During acute rehabilitation, the overall amount of UL activity and the active distance wheeled significantly increased in tetraplegic patients, but remained constant in paraplegic patients. The same tendency was shown in clinical scores with the exception of those for independence, which showed improvements at the beginning of the rehabilitation period, even in paraplegic subjects. In the later stages of acute rehabilitation, the quantity of UL activity in tetraplegic individuals matched that of their paraplegic counterparts, despite their greater motor impairments. Both subject groups showed higher UL activity during therapy time compared to the time outside of therapy time. CONCLUSION: Tracking day-to-day UL activity is necessary to gain insights into the real impact of a patient's impairments on their UL movements during therapy and during their leisure time. In the future, this novel methodology may be used to reliably control and adjust ABRT and to evaluate the progress of UL rehabilitation in clinical trials.

Novel Sensor Technology To Assess Independence and Limb-Use Laterality in Cervical Spinal Cord Injury.

After spinal cord injury (SCI), levels of independence are commonly assessed with standardized clinical assessments. However, such tests do not provide information about the actual extent of upper limb activities or the impact on independence of bi- versus unilateral usage throughout daily life following cervical SCI. The objective of this study was to correlate activity intensity and laterality of upper extremity activity measured by body-fixed inertial measurement units (IMUs) with clinical assessment scores of independence. Limb-use intensity and laterality of activities performed by the upper extremities was measured in 12 subjects with cervical SCI using four IMUs (positioned on both wrists, on the chest, and on one wheel of the wheelchair). Algorithms capable of reliably detecting self-propulsion and arm activity in a clinical environment were applied to rate functional outcome levels, and were related to clinical independence measures during inpatient rehabilitation. Measures of intensity of upper extremity activity during self-propulsion positively correlated (p < 0.05, r = 0.643) with independence measures related to mobility. Clinical measures of laterality were positively correlated (p < 0.01, r = 0.900) with laterality as measured by IMUs during "daily life," and increased laterality was negatively correlated (p < 0.01, r = -0.739) with independence. IMU sensor technology is sensitive in assessing and quantifying upper limb-use intensity and laterality in human cervical SCI. Continuous and objective movement data of distinct daily activities (i.e., mobility and day-to-day activities) can be related to levels of independence. Therefore, IMU sensor technology is suitable not only for monitoring activity levels during rehabilitation (including during clinical trials) but could also be used to assess levels of participation after discharge.