Nerve Transfer After Cervical Spinal Cord Injury: Who Has a "Time Sensitive" Injury Based on Electrodiagnostic Findings?

OBJECTIVE: To use the ulnar compound muscle action potential (CMAP) to abductor digiti minimi (ADM) to identify the proportion of individuals with cervical spinal cord injury (SCI) who have lower motor neuron (LMN) abnormalities involving the C8-T1 spinal nerve roots, within 3-6 months, and thus may influence the response to nerve transfer surgery. DESIGN: Retrospective analysis of prospectively collected data. Data were analyzed from European Multicenter Study About SCI database. SETTING: Multi-center, academic hospitals. PARTICIPANTS: We included 79 subjects (age=41.4±17.7, range:16-75; 59 men; N=79), who were classified as cervical level injuries 2 weeks after injury and who had manual muscle strength examinations that would warrant consideration for nerve transfer (C5≥4, C8<3). INTERVENTIONS: None. MAIN OUTCOME MEASURES: The ulnar nerve CMAP amplitude to ADM was used as a proxy measure for C8-T1 spinal segment health. CMAP amplitude was stratified into very abnormal (<1.0 mV), sub-normal (1.0-5.9 mV), and normal (>6.0 mV). Analysis took place at 3 (n=148 limbs) and 6 months (n=145 limbs). RESULTS: At 3- and 6-month post-injury, 33.1% and 28.3% of limbs had very abnormal CMAP amplitudes, respectively, while in 54.1% and 51.7%, CMAPs were sub-normal. Median change in amplitude from 3 to 6 months was 0.0 mV for very abnormal and 1.0 mV for subnormal groups. A 3-month ulnar CMAP <1 mV had a positive predictive value of 0.73 (95% CI 0.69-0.76) and 0.78 (95% CI 0.75-0.80) for C8 and T1 muscle strength of 0 vs 1 or 2. CONCLUSION: A high proportion of individuals have ulnar CMAPs below the lower limit of normal 3- and 6-month post cervical SCI and may also have intercurrent LMN injury. Failure to identify individuals with LMN denervation could result in a lost opportunity to improve hand function through timely nerve transfer surgeries.

A Grain Orientation-Independent Single-Step Saw Damage Gettering/Wet texturing Process for Efficient Silicon Solar Cells.

Improving electrical and optical properties is important in manufacturing high-efficiency solar cells. Previous studies focused on individual gettering and texturing methods to improve solar cell material quality and reduce reflection loss, respectively. This study presents a novel method called saw damage gettering with texturing that effectively combines both methods for multicrystalline silicon (mc-Si) wafers manufactured using the diamond wire sawing (DWS) method. Although mc-Si is not the Si material currently used in photovoltaic products, the applicability of this method using the mc-Si wafers as it contains all grain orientations is demonstrated. It utilizes saw damage sites on the wafer surfaces for gettering metal impurities during annealing. Additionally, it can crystallize amorphous silicon on wafer surfaces generated during the sawing process to allow conventional acid-based wet texturing. This texturing method and annealing for 10 min allow for the removal of metal impurities and effectively forms a textured DWS Si wafer. The results show that the open-circuit voltage (ΔVoc  = +29 mV), short-circuit current density (ΔJsc  = +2.5 mA cm-2 ), and efficiency (Δη = +2.1%) improved in the p-type passivated emitter and rear cells (p-PERC) manufactured using this novel method, as compared to those in the reference solar cells.

Fourier modal method for inverse design of metasurface-enhanced micro-LEDs.

We present a simulation capability for micro-scale light-emitting diodes (µLEDs) that achieves comparable accuracy to CPU-based finite-difference time-domain simulation but is more than 107 times faster. Our approach is based on the Fourier modal method (FMM)-which, as we demonstrate, is well suited to modeling thousands of incoherent sources-with extensions that allow rapid convergence for µLED structures that are challenging to model with standard approaches. The speed of our method makes the inverse design of µLEDs tractable, which we demonstrate by designing a metasurface-enhanced µLED that doubles the light extraction efficiency of an unoptimized device.

Intramuscular coherence enables robust assessment of modulated supra-spinal input in human gait: an inter-dependence study of visual task and walking speed.

Intramuscular high-frequency coherence is increased during visually guided treadmill walking as a consequence of increased supra-spinal input. The influence of walking speed on intramuscular coherence and its inter-trial reproducibility need to be established before adoption as a functional gait assessment tool in clinical settings. Here, fifteen healthy controls performed a normal and a target walking task on a treadmill at various speeds (0.3 m/s, 0.5 m/s, 0.9 m/s, and preferred) during two sessions. Intramuscular coherence was calculated between two surface EMG recordings sites of the Tibialis anterior muscle during the swing phase of walking. The results were averaged across low-frequency (5-14 Hz) and high-frequency (15-55 Hz) bands. The effect of speed, task, and time on mean coherence was assessed using three-way repeated measures ANOVA. Reliability and agreement were calculated with the intra-class correlation coefficient and Bland-Altman method, respectively. Intramuscular coherence during target walking was significantly higher than during normal walking across all walking speeds in the high-frequency band as obtained by the three-way repeated measures ANOVA. Interaction effects between task and speed were found for the low- and high-frequency bands, suggesting that task-dependent differences increase at higher walking speeds. Reliability of intramuscular coherence was moderate to excellent for most normal and target walking tasks in all frequency bands. This study confirms previous reports of increased intramuscular coherence during target walking, while providing first evidence for reproducibility and robustness of this measure as a requirement to investigate supra-spinal input.Trial registration Registry number/ClinicalTrials.gov Identifier: NCT03343132, date of registration 2017/11/17.

Incidence and Risk Factors of Pneumonia in Individuals With Acute Spinal Cord Injury: A Multi-national, Multi-center, Prospective Cohort Study.

OBJECTIVE: To describe the occurrence of pneumonia in individuals with acute spinal cord injury (SCI) and identify its key predictors. DESIGN: Multi-centric, longitudinal cohort study. SETTING: 10 specialized SCI rehabilitation units in Europe and Australia. PARTICIPANTS: Eligible were 902 men and women with acute SCI, aged 18 years or older, with cervical or thoracic lesions and not dependent on 24-hour mechanical ventilation; 503 participated in the study (N=503). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We assessed demographics and lesion related parameters at study entry, and any pneumonia events throughout inpatient rehabilitation. Respiratory function, decubitus, and urinary tract infections were assessed at 1, 3, and 6 months post injury as well as at discharge from inpatient rehabilitation. Time to event (pneumonia) analyses were done using the Kaplan-Meier method, and potential predictors for pneumonia were analyzed with multivariable survival models. RESULTS: Five hundred three patients with SCI were included, with 70 experiencing at least 1 pneumonia event. 11 participants experienced 2 or more events during inpatient rehabilitation. Most events occurred very early after injury, with a median of 6 days. Pneumonia risk was associated with tetraplegia (hazard ratio [HR]=1.78; 95% confidence interval [CI] 1.00-3.17) and traumatic etiology (HR=3.75; 95% CI 1.30-10.8) American Spinal Injury Impairment Scale (AIS) A (HR=5.30; 95% CI 2.28-12.31), B (HR=4.38; 95% CI 1.77-10.83), or C (HR=4.09; 95% CI 1.71-9.81) lesions. For every 10 cmH2O increase in inspiratory muscle strength, pneumonia risk was reduced by 13% (HR=0.87; 95% CI 0.78-0.97). CONCLUSION: Pneumonia is a major complication after SCI with the highest incidence very early after injury. Individuals with traumatic or AIS A, B, or C tetraplegia are at highest risk for pneumonia.

Use of professional home care in persons with spinal cord injury in Switzerland: a cross-sectional study.

BACKGROUND: Persons with spinal cord injury (SCI) living in the community often require care. The boundaries between professional home care and informal care are blurred, and it is unclear who the typical user of home care is. The objective of this study was to describe the characteristics of persons with SCI using professional home care in Switzerland, determine the frequency of home care visits, and investigate the association of sociodemographic factors, SCI-specific characteristics, secondary health conditions, and functional independence with the use of home care. METHODS: We used cross-sectional data from the 2017 community survey of the Swiss Spinal Cord Injury Cohort Study (SwiSCI). Out of 3,959 eligible individuals 1294 completed the questionnaire and were included in the analysis (response rate 33%). Using descriptive statistics, differences between home care users and non-users as well as the frequency of home care visits were investigated. The association between sociodemographic factors, SCI-specific characteristics, secondary health conditions, functional independence and the use of home care was analyzed using multivariable logistic regression. Multiple imputation was used to account for missing data. RESULTS: Of 1,294 participants, 280 (22%) used professional home care. The median weekly professional home care duration was 6 h (Q1 = 2, Q3 = 12). More home care was used in persons with lower functional independence (Odds ratio (OR) 0.30 per 10 unit decrease in the Spinal Cord Independence Measure, 95%-Confidence interval (CI) 0.24-0.37), fewer secondary health conditions (OR 0.96 per unit Spinal Cord Injury Secondary Conditions Scale, 95%-CI 0.94-0.99), tetraplegia (OR 2.77, 95%-CI 1.92-4.00), women (OR 2.42, 95%-CI 1.70-3.43), higher age (OR 1.22 per 10 years increase, 95%-CI 1.06-1.39), living alone (OR 2.48, 95%-CI 1.53-4.03), and those receiving support from an informal caregiver (OR 1.88, 95%-CI 1.27-2.77). CONCLUSIONS: This is the first study to examine the use of professional home care from the perspective of persons with SCI in Switzerland. Lower functional independence strongly predicts increased home care use. The findings showed that professional home care complements informal care and is more likely to be used by individuals with SCI who live alone, have tetraplegia, and are female.

Queckenstedt's test repurposed for the quantitative assessment of the cerebrospinal fluid pulsatility curve.

PURPOSE: Before the era of spinal imaging, presence of a spinal canal block was tested through gross changes in cerebrospinal fluid pressure (CSFP) provoked by manual compression of the jugular veins (referred to as Queckenstedt's test; QT). Beyond these provoked gross changes, cardiac-driven CSFP peak-to-valley amplitudes (CSFPp) can be recorded during CSFP registration. This is the first study to assess whether the QT can be repurposed to derive descriptors of the CSF pulsatility curve, focusing on feasibility and repeatability. METHOD: Lumbar puncture was performed in lateral recumbent position in fourteen elderly patients (59.7±9.3 years, 6F) (NCT02170155) without stenosis of the spinal canal. CSFP was recorded during resting state and QT. A surrogate for the relative pulse pressure coefficient was computed from repeated QTs (i.e., RPPC-Q). RESULTS: Resting state mean CSFP was 12.3 mmHg (IQR 3.2) and CSFPp was 1.0 mmHg (0.5). Mean CSFP rise during QT was 12.5 mmHg (7.3). CSFPp showed an average 3-fold increase at peak QT compared to the resting state. Median RPPC-Q was 0.18 (0.04). There was no systematic error in the computed metrics between the first and second QT. CONCLUSION: This technical note describes a method to reliably derive, beyond gross CSFP increments, metrics related to cardiac-driven amplitudes during QT (i.e., RPPC-Q). A study comparing these metrics as obtained by established procedures (i.e., infusion testing) and by QT is warranted.

International surveillance study in acute spinal cord injury confirms viability of multinational clinical trials.

BACKGROUND: The epidemiological international landscape of traumatic spinal cord injury (SCI) has evolved over the last decades along with given inherent differences in acute care and rehabilitation across countries and jurisdictions. However, to what extent these differences may influence neurological and functional recovery as well as the integrity of international trials is unclear. The latter also relates to historical clinical data that are exploited to inform clinical trial design and as potential comparative data. METHODS: Epidemiological and clinical data of individuals with traumatic and ischemic SCI enrolled in the European Multi-Center Study about Spinal Cord Injury (EMSCI) were analyzed. Mixed-effect models were employed to account for the longitudinal nature of the data, efficiently handle missing data, and adjust for covariates. The primary outcomes comprised demographics/injury characteristics and standard scores to quantify neurological (i.e., motor and sensory scores examined according to the International Standards for the Neurological Classification of Spinal Cord Injury) and functional recovery (walking function). We externally validated our findings leveraging data from a completed North American landmark clinical trial. RESULTS: A total of 4601 patients with acute SCI were included. Over the course of 20 years, the ratio of male to female patients remained stable at 3:1, while the distribution of age at injury significantly shifted from unimodal (2001/02) to bimodal distribution (2019). The proportional distribution of injury severities and levels remained stable with the largest percentages of motor complete injuries. Both, the rate and pattern of neurological and functional recovery, remained unchanged throughout the surveillance period despite the increasing age at injury. The findings related to recovery profiles were confirmed by an external validation cohort (n=791). Lastly, we built an open-access and online surveillance platform ("Neurosurveillance") to interactively exploit the study results and beyond. CONCLUSIONS: Despite some epidemiological changes and considerable advances in clinical management and rehabilitation, the neurological and functional recovery following SCI has remained stable over the last two decades. Our study, including a newly created open-access and online surveillance tool, constitutes an unparalleled resource to inform clinical practice and implementation of forthcoming clinical trials targeting neural repair and plasticity in acute spinal cord injury.

EXPANSIN A1-mediated radial swelling of pericycle cells positions anticlinal cell divisions during lateral root initiation.

In plants, postembryonic formation of new organs helps shape the adult organism. This requires the tight regulation of when and where a new organ is formed and a coordination of the underlying cell divisions. To build a root system, new lateral roots are continuously developing, and this process requires the tight coordination of asymmetric cell division in adjacent pericycle cells. We identified EXPANSIN A1 (EXPA1) as a cell wall modifying enzyme controlling the divisions marking lateral root initiation. Loss of EXPA1 leads to defects in the first asymmetric pericycle cell divisions and the radial swelling of the pericycle during auxin-driven lateral root formation. We conclude that a localized radial expansion of adjacent pericycle cells is required to position the asymmetric cell divisions and generate a core of small daughter cells, which is a prerequisite for lateral root organogenesis.

Mind your step: Target walking task reveals gait disturbance in individuals with incomplete spinal cord injury.

BACKGROUND: Walking over obstacles requires precise foot placement while maintaining balance control of the center of mass (CoM) and the flexibility to adapt the gait patterns. Most individuals with incomplete spinal cord injury (iSCI) are capable of overground walking on level ground; however, gait stability and adaptation may be compromised. CoM control was investigated during a challenging target walking (TW) task in individuals with iSCI compared to healthy controls. The hypothesis was that individuals with iSCI, when challenged with TW, show a lack of gait pattern adaptability which is reflected by an impaired adaptation of CoM movement compared to healthy controls. METHODS: A single-center controlled diagnostic clinical trial with thirteen participants with iSCI (0.3-24 years post injury; one subacute and twelve chronic) and twelve healthy controls was conducted where foot and pelvis kinematics were acquired during two conditions: normal treadmill walking (NW) and visually guided target walking (TW) with handrail support, during which participants stepped onto projected virtual targets synchronized with the moving treadmill surface. Approximated CoM was calculated from pelvis markers and used to calculate CoM trajectory length and mean CoM Euclidean distance TW-NW (primary outcome). Nonparametric statistics, including spearman rank correlations, were performed to evaluate the relationship between clinical parameter, outdoor mobility score, performance, and CoM parameters (secondary outcome). RESULTS: Healthy controls adapted to TW by decreasing anterior-posterior and vertical CoM trajectory length (p < 0.001), whereas participants with iSCI reduced CoM trajectory length only in the vertical direction (p = 0.002). Mean CoM Euclidean distance TW-NW correlated with participants' neurological level of injury (R = 0.76, p = 0.002) and CoM trajectory length (during TW) correlated with outdoor mobility score (R = - 0.64, p = 0.026). CONCLUSIONS: This study demonstrated that reduction of CoM movement is a common strategy to cope with TW challenge in controls, but it is impaired in individuals with iSCI. In the iSCI group, the ability to cope with gait challenges worsened the more rostral the level of injury. Thus, the TW task could be used as a gait challenge paradigm in ambulatory iSCI individuals. Trial registration Registry number/ ClinicalTrials.gov Identifier: NCT03343132, date of registration 2017/11/17.

Opposite Regulation of Homer Signal at the NMJ Postsynaptic Micro Domain between Slow- and Fast-Twitch Muscles in an Experimentally Induced Autoimmune Myasthenia Gravis (EAMG) Mouse Model.

Accelerated postsynaptic remodelling and disturbance of neuromuscular transmission are common features of autoimmune neurodegenerative diseases. Homer protein isoform expression, crosslinking activity and neuromuscular subcellular localisation are studied in mouse hind limb muscles of an experimentally induced autoimmune model of Myasthenia Gravis (EAMG) and correlated to motor end plate integrity. Soleus (SOL), extensor digitorum longus (EDL) and gastrocnemius (GAS) skeletal muscles are investigated. nAChR membrane clusters were studied to monitor neuromuscular junction (NMJ) integrity. Fibre-type cross-sectional area (CSA) analysis is carried out in order to determine the extent of muscle atrophy. Our findings clearly showed that crosslinking activity of Homer long forms (Homer 1b/c and Homer2a/b) are decreased in slow-twitch and increased in fast-twitch muscle of EAMG whereas the short form of Homer that disrupts Homer crosslinking (Homer1a) is upregulated in slow-twitch muscle only. Densitometry analysis showed a 125% increase in Homer protein expression in EDL, and a 45% decrease in SOL of EAMG mice. In contrast, nAChR fluorescence pixel intensity decreased in endplates of EAMG mice, more distinct in type-I dominant SOL muscle. Morphometric CSA of EAMG vs. control (CTR) revealed a significant reduction in EDL but not in GAS and SOL. Taken together, these results indicate that postsynaptic Homer signalling is impaired in slow-twitch SOL muscle from EAMG mice and provide compelling evidence suggesting a functional coupling between Homer and nAChR, underscoring the key role of Homer in skeletal muscle neurophysiology.

Wallerian degeneration in cervical spinal cord tracts is commonly seen in routine T2-weighted MRI after traumatic spinal cord injury and is associated with impairment in a retrospective study.

OBJECTIVES: Wallerian degeneration (WD) is a well-known process after nerve injury. In this study, occurrence of remote intramedullary signal changes, consistent with WD, and its correlation with clinical and neurophysiological impairment were assessed after traumatic spinal cord injury (tSCI). METHODS: In 35 patients with tSCI, WD was evaluated by two radiologists on T2-weighted images of serial routine MRI examinations of the cervical spine. Dorsal column (DC), lateral corticospinal tract (CS), and lateral spinothalamic tract (ST) were the analyzed anatomical regions. Impairment scoring according to the American Spinal Injury Association Impairment Scale (AIS, A-D) as well as a scoring system (0-4 points) for motor evoked potential (MEP) and sensory evoked potential (SEP) was included. Mann-Whitney U test was used to test for differences. RESULTS: WD in the DC occurred in 71.4% (n = 25), in the CS in 57.1% (n = 20), and in 37.1% (n = 13) in the ST. With WD present, AIS grades were worse for all tracts. DC: median AIS B vs D, p < 0.001; CS: B vs D, p = 0.016; and ST: B vs D, p = 0.015. More pathological MEP scores correlated with WD in the DC (median score 0 vs 3, p < 0.001) and in the CS (0 vs 2, p = 0.032). SEP scores were lower with WD in the DC only (1 vs 2, p = 0.031). CONCLUSIONS: WD can be detected on T2-weighted scans in the majority of cervical spinal cord injury patients and should be considered as a direct effect of the trauma. When observed, it is associated with higher degree of impairment. KEY POINTS: • Wallerian degeneration is commonly seen in routine MRI after traumatic spinal cord injury. • Wallerian degeneration is visible in the anatomical regions of the dorsal column, the lateral corticospinal tract, and the lateral spinothalamic tract. • Presence of Wallerian degeneration is associated with higher degree of impairment.

Detrusor sphincter dyssynergia: can a more specific definition distinguish between patients with and without an underlying neurological disorder?

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To evaluate if specific definitions of detrusor sphincter dyssynergia (DSD) might distinguish between individuals with spinal cord injury (SCI) and those with no underlying neurological disorder (NO ND). SETTING: Single tertiary university SCI center. METHODS: A series of 153 individuals, 81 with traumatic SCI and 72 with NO ND, were prospectively evaluated and included in this study. All individuals underwent a clinical neuro-urological examination, a neurophysiological work-up and a video-urodynamic investigation and were diagnosed with DSD as defined by the International Continence Society (ICS). We determined the DSD grades/types according to the classifications by Yalla (grade 1-3), Blaivas (type 1-3) and Weld (type 1-2). Distribution of the DSD grades/types were compared between SCI and NO ND individuals. Associations between the various DSD grades/types and clinical parameters, such as risk factors for upper urinary tract damage (all individuals) or lower extremity motor scores, SCI injury levels and severity scores (only SCI group), were assessed. RESULTS: The distribution of all DSD types were similar between groups (p > 0.05). None of the DSD classifications allowed risk assessment for upper urinary tract damage. A significant association between DSD type and other clinical parameters could not be found (p > 0.05). CONCLUSIONS: None of the investigated DSD definitions can distinguish between patients with SCI and with NO ND. The more complex DSD classifications by Yalla, Blaivas or Weld cannot compete with the ICS binary yes-no definition which is pragmatic and straightforward for managing patients in daily clinical practice. SPONSORSHIP: None.

Etiology-specific variation in survival following non-traumatic spinal cord injury: a causal inference approach using data from a population-based cohort.

STUDY DESIGN: Observational, population-based cohort study. OBJECTIVES: To evaluate the origin and contribution to excess of survival differences following non-traumatic spinal cord injury (NTSCI) using etiology as proxy for variation in underlying health condition. SETTING: Specialized rehabilitation centers in Switzerland. METHODS: Medical record data collected by the Swiss Spinal Cord Injury cohort (SwiSCI) study were linked with mortality information from the Swiss National Cohort. Considering contemporary theory and empirical evidence, a directed acyclic graph (DAG) was developed to formally evaluate causal differences among NTSCI etiologies, relative to traumatic SCI (TSCI). Statistical inference was contingent on hazard ratios (HRs) and marginal survival differences, derived using flexible parametric modeling. RESULTS: 3643 individuals (NTSCI = 1357; TSCI = 2286) diagnosed with SCI between 1990 and 2011 were included, contributing a cumulative 41,344 person-years and 1323 deaths. Test statistics confirmed DAG-dataset consistency. As compared to TSCI, mortality was elevated in all NTSCI etiological groups; malignant etiologies had the highest HRs (10; 95% CI, 8.0 to 14) followed by infection (2.6; 1.8 to 3.6) and vascular (2.5; 2.0 to 3.2) etiology groups. At the attained age of 55, the estimated reduction in survival among non-malignant etiologies was 9.4% (5.8 to 13) at 5 years and 17% (11 to 23) at 20 years. CONCLUSIONS: Causal differences in survival among NTSCI etiological groups are likely a result of chronic variation in health conditions. This study supports the development of long-term interdisciplinary management and policy for individuals with NTSCI, specific to etiology.

Self-reports of treatment for secondary health conditions: results from a longitudinal community survey in spinal cord injury.

STUDY DESIGN: Longitudinal community survey. OBJECTIVES: To describe the treatment for secondary health conditions as reported by individuals living with spinal cord injury (SCI) and to identify potential predictors of treatment. SETTING: Community (people with SCI living in Switzerland). METHODS: Data on the frequency, severity, and treatment of 14 common health conditions (HCs) in the past three months were collected in two surveys by the Swiss Spinal Cord Injury (SwiSCI) cohort study, in 2012 and 2017. Variation in treatment was analyzed using descriptive statistics, by survey period and severity of HC. Conditional multilevel random-effects logistic regression was used to describe differences in self-reported treatment with respect to sociodemographic and socioeconomic factors in addition to SCI characteristics and severity and number of HCs. RESULTS: Severe or chronic autonomic dysreflexia and sleep problems showed in the self-report as the HCs with the lowest occurrence/frequency of treatment. Across all HCs, higher age, shorter time since injury, the total number of HCs, and level of severity were associated with a higher propensity for reporting treatment. Individuals with severe financial difficulties additionally had 1.40 greater odds of receiving treatment (95% CI 1.09-1.80). CONCLUSIONS: This study identified systematic differences in the report of HCs and their treatment within the Swiss SCI community. This study thus provides a basis to guide future research on identifying targets of intervention for long-term clinical management of SCI.

Optimizing clinical trial design using prospective cohort study data: a case study in neuro-urology.

STUDY DESIGN: Simulations using data from a prospective cohort study. OBJECTIVES: To illustrate how prospective cohort data can be employed in randomized controlled trial (RCT) planning to assess feasibility and operational challenges, using TASCI (Transcutaneous tibial nerve stimulation in patients with Acute Spinal Cord Injury to prevent neurogenic detrusor overactivity: a nationwide randomized, sham-controlled, double-blind clinical trial) as a case study. SETTING: Spinal cord injury (SCI) rehabilitation centers in Switzerland. METHODS: TASCI is nested in the multicenter Swiss Spinal Cord Injury Cohort Study (SwiSCI), which prospectively includes patients with acute SCI. In simulations, data from 640 patients, collected by SwiSCI, were used to investigate different scenarios of patient eligibility and study consent, as well as the performance of the randomization list. Descriptive analysis was used to describe the population of interest and the simulation results; multivariable logistic regression analysis was performed to identify predictors of discharge within the TASCI intervention time period. RESULTS: The recruitment target of 114 patients is obtainable within the originally envisioned 3-year time period under the most favorable recruitment scenario examined. The distribution of the primary prognostic factor produced imbalance in the randomization lists and informed further discussion of the cut-off values used in stratification. Influxes of patients resulted in overlapping intervention periods for multiple participants, which guided resource allocation. Early discharge was related to the primary prognostic factor and study center, but is only anticipated in about 8% of participants. CONCLUSIONS: Prospective cohort data are a very valuable resource for planning RCTs.

Safety and Feasibility of Lumbar Cerebrospinal Fluid Pressure and Intraspinal Pressure Studies in Cervical Stenosis: A Case Series.

INTRODUCTION: Degenerative cervical myelopathy (DCM) leads to functional impairment by compression of the spinal cord and nerve roots. In DCM, the dynamics of cerebrospinal fluid pressure (CSFP) and intraspinal pressure (ISP), as well as spinal cord perfusion pressure (SCPP) remain not investigated yet. Recent technical advances have enabled investigation of these parameters in acute spinal cord injury (SCI). We aim to investigate the properties of CSFP/ISP and spinal cord hemodynamics during and after decompressive surgery in DCM. MATERIALS AND METHODS: Four patients with DCM were enrolled; during surgery and 24 h postoperative, ISP at level was measured in one patient, and CSFP was measured in two patients. In one patient, CSFP was recorded at bedside before surgery. RESULTS: All measurements were conducted without adverse events and were well tolerated. With CSFP analysis, post-decompression Queckenstedt's test was responsive in two patients (i.e., jugular vein compression resulted in an elevation of CSFP pressure). In the patient whose CSFP was tested at bedside, Queckenstedt's test was not responsive before decompression. Individual optimum SCPPs were calculated to be between 70 and 75 mmHg. CONCLUSION: ISP and CSFP can reflect spinal compression and sufficient decompression. A better understanding and systematic monitoring possibly lead to improved hemodynamic management and may allow early recognition of postoperative complications such as swelling and bleeding.

Hand or foot train-of-four tests and surgical site muscle relaxation assessed with multiple motor evoked potentials: A prospective observational study.

BACKGROUND: Intra-operative muscle relaxation is often required in orthopaedic surgery and the hand train-of-four (TOF) test is usually used for its quantification. However, even though full muscle relaxation is claimed by anaesthesiologists based on a TOF count of zero, surgeons observe residual muscle activity. OBJECTIVE: The aim of the study was to assess if hand or foot TOF adequately represents intra-operative muscle relaxation compared with multiple motor evoked potentials. DESIGN: Prospective observational study. SETTING: A single-centre study performed between February 2016 and December 2018 at the Balgrist University Hospital, Zurich, Switzerland. PATIENTS: Twenty patients scheduled for elective lumbar spinal fusion were prospectively enrolled in this study after giving written informed consent. INTERVENTIONS: To assess neuromuscular blockade (NMB) with the intermediate duration nondepolarising neuromuscular blocking agent rocuronium, hand TOF (adductor pollicis) and foot TOF (flexor hallucis brevis) monitoring, and muscle motor evoked potentials (MMEPs) from the upper and lower extremities were assessed prior to surgery under general anaesthesia. Following baseline measurements, muscle relaxation was performed with rocuronium until the spinal surgeon observed sufficient relaxation for surgical intervention. At this timepoint, NMB was assessed by TOF and MMEP. MAIN OUTCOME MEASURES: The primary outcome was to determine the different effect of rocuronium on muscle relaxation comparing hand and foot TOF with the paraspinal musculature assessed by MMEP. RESULTS: Hand TOF was more resistant to NMB and had a shorter recovery time than foot TOF. When comparing MMEPs, muscle relaxation occurred first in the hip abductors, and the paraspinal and deltoid muscles. The most resistant muscle to NMB was the abductor digiti minimi. Direct comparison showed that repetitive MMEPs simultaneously recorded from various muscles at the upper and lower extremities and from paraspinal muscles reflect muscle relaxation similar to TOF testing. CONCLUSION: Hand TOF is superior to foot TOF in assessing muscle relaxation during spinal surgery. Hand TOF adequately represents the degree of muscle relaxation not only for the paraspinal muscles but also for all orthopaedic surgical sites where NMB is crucial for good surgical conditions. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03318718).

Deltoid muscle contribution to shoulder flexion and abduction strength: an experimental approach.

BACKGROUND: The rotator cuff (RC) and the deltoid muscle are 2 synergistic units that enable the functionally demanding movements of the shoulder. A number of biomechanical studies assume similar force contribution of the force couple (RC and deltoid) over the whole range of motion, whereas others propose position-dependent force distribution. There is a lack of in vivo data regarding the deltoid's contribution to shoulder flexion and abduction strength. This study aimed to create reliable in vivo data quantifying the deltoid's contribution to shoulder flexion and abduction strength throughout the range of motion. METHODS: Active range of motion and isometric muscle strength of shoulder abduction and flexion in 0°, 30°, 60°, 90°, and 120° of abduction/flexion as well as internal and external rotation in 0° and 90° of abduction were obtained in 12 healthy volunteers on the dominant arm before and after an ultrasound-guided isolated axillary nerve block. Needle electromyography was performed before and after the block to confirm deltoid paralysis. Radiographs of the shoulder and an ultrasonographic examination were used to exclude relevant shoulder pathologies. RESULTS: Active range of motion showed a minimal to moderate reduction to 94% and 88% of the preintervention value for abduction and flexion. Internal and external rotation amplitude was not impaired. The abduction strength was significantly reduced to 76% at 0° (P = .002) and to 25% at 120° (P < .001) of abduction. The flexion strength was significantly reduced to 64% at 30° (P < .001) and to 30% at 120° (P < .001) of flexion. The strength reduction was linear, depending on the flexion/abduction angle. The maximal external rotation strength showed a significant decrease to 53% in 90° (P < .001) of abduction, whereas in adduction no strength loss was observed (P = .09). The internal rotation strength remained unaffected in 0° and 90° of abduction (P = .28; P = .13). CONCLUSION: The deltoid shows a linear contribution to maximal shoulder strength depending on the abduction or flexion angle, ranging from 24% in 0° to 75% in 120° of abduction and from 11% in 0° to 70% in 120° of flexion, respectively. The overall contribution to abduction strength is higher than to flexion strength. The combination of deltoid muscle and teres minor contributes about 50% to external rotation strength in 90° of abduction. The internal rotation strength is not influenced by a deltoid paralysis. This study highlights the position-dependent contribution of the shoulder muscles to strength development and thereby provides an empirical approach to better understand human shoulder kinematics.

The Peroxisome Proliferator-Activated Receptor (PPAR)-γ Antagonist 2-Chloro-5-Nitro-N-Phenylbenzamide (GW9662) Triggers Perilipin 2 Expression via PPARδ and Induces Lipogenesis and Triglyceride Accumulation in Human THP-1 Macrophages.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor family, playing pivotal roles in regulating glucose and lipid metabolism as well as inflammation. While characterizing potential PPARγ ligand activity of natural compounds in macrophages, we investigated their influence on the expression of adipophilin [perilipin 2 (PLIN2)], a well-known PPARγ target. To confirm that a compound regulates PLIN2 expression via PPARγ, we performed experiments using the widely used PPARγ antagonist 2-chloro-5-nitro-N-phenylbenzamide (GW9662). Surprisingly, instead of blocking upregulation of PLIN2 expression in THP-1 macrophages, expression was concentration-dependently induced by GW9662 at concentrations and under conditions commonly used. We found that this unexpected upregulation occurs in many human and murine macrophage cell models and also primary cells. Profiling expression of PPAR target genes showed upregulation of several genes involved in lipid uptake, transport, and storage as well as fatty acid synthesis by GW9662. In line with this and with upregulation of PLIN2 protein, GW9662 elevated lipogenesis and increased triglyceride levels. Finally, we identified PPARδ as a mediator of the substantial unexpected effects of GW9662. Our findings show that: 1) the PPARγ antagonist GW9662 unexpectedly activates PPARδ-mediated signaling in macrophages, 2) GW9662 significantly affects lipid metabolism in macrophages, 3) careful validation of experimental conditions and results is required for experiments involving GW9662, and 4) published studies in a context comparable to this work may have reported erroneous results if PPARγ independence was demonstrated using GW9662 only. In light of our findings, certain existing studies might require reinterpretation regarding the role of PPARγ SIGNIFICANCE STATEMENT: Peroxisome proliferator-activated receptors (PPARs) are targets for the treatment of various diseases, as they are key regulators of inflammation as well as lipid and glucose metabolism. Hence, reliable tools to characterize the molecular effects of PPARs are indispensable. We describe profound and unexpected off-target effects of the PPARγ antagonist 2-chloro-5-nitro-N-phenylbenzamide (GW9662) involving PPARδ and in turn affecting macrophage lipid metabolism. Our results question certain existing studies using GW9662 and make better experimental design of future studies necessary.