Higher Regional Gray Matter Volume and White Matter Integrity in Individuals With Central Neuropathic Pain After Spinal Cord Injury.

Spinal cord injury (SCI) is a debilitating neurological condition that often leads to central neuropathic pain (CNP). As the fundamental mechanism of CNP is not fully established, its management is one of the most challenging problems among people with SCI. To shed more light on CNP mechanisms, the aim of this cross-sectional study was to compare the brain structure between individuals with SCI and CNP and those without CNP by examining the gray matter (GM) volume and the white matter (WM) integrity. Fifty-two individuals with SCI-28 with CNP and 24 without CNP-underwent a magnetic resonance imaging (MRI) session, including a T1-weighted scan for voxel-based morphometry, and a diffusion-weighted imaging (DWI) scan for WM integrity analysis, as measured by fractional anisotropy (FA) and mean diffusivity (MD). We found significantly higher GM volume in individuals with CNP compared with pain-free individuals in the right superior (p < 0.0014) and middle temporal gyri (p < 0.0001). Moreover, individuals with CNP exhibited higher WM integrity in the splenium of the corpus callosum (p < 0.0001) and in the posterior cingulum (p < 0.0001), compared with pain-free individuals. The results suggest that the existence of CNP following SCI is associated with GM and WM structural abnormalities in regions involved in pain intensification and spread, and which may reflect maladaptive neural plasticity in CNP.

Reliability and validity of the Hebrew version of the International Spinal Cord Injury Activities and Participation Basic Data Set.

BACKGROUND: The International Spinal Cord Injury (SCI) Activities and Participation Basic Data Set (APBDS) was created to facilitate comparisons of levels of function and disability in SCI individuals worldwide. AIM: Evaluating the reliability and validity of the APBDS's Hebrew translation was our goal. DESIGN: Observational, cross-sectional study. SETTING: University and Outpatient Rehabilitation Department of a Medical Center. POPULATION: Individuals with spinal cord injury (SCI). METHODS: The APBDS's Hebrew version was administered to fifty individuals with SCI. Reliability was evaluated through Cronbach Alpha Test and a test-retest method. Validity was determined by testing for convergence with the World Health Organization Disability Assessment Scale (WHODAS) 2.0 and the Medical Outcomes Short Form Health Survey (SF-12). RESULTS: The Hebrew APBDS had a high test-retest reliability (ICC=0.792) and an adequate Cronbach alpha test (α=0.792). Significant convergent validity was partial with both the WHODAS 2.0 (strong in the self-care objective (r=-0.648) and subjective (r=-0.666), moderate in the total objective (r=-0.640) and subjective (r=-0.570) domains of the APBDS) and the SF-12 (moderate between the total objective domain and the Physical composite score (r=0.378), poor with the Mental composite score (r=0.310)). CONCLUSIONS: Although the Hebrew APBDS's moderate reliability and validity warrants further research, it opens new vistas regarding assessment of SCI individuals' satisfaction, activity, and participation. CLINICAL REHABILITATION IMPACT: We feel that this data set may be used in the long-term follow-up of SCI individuals in the Sheba SCI rehabilitation registry.

Determinants of Quality of Life in Individuals With Spinal Cord Injury Using Structural Equation Modeling.

OBJECTIVE: The objective of this study is to examine the interdependent associations between International Classification of Functioning, Disability and Health (ICF) domains and their relationship with environmental factors with regard to quality of life (QoL) in individuals with spinal cord injury (SCI). DESIGN: Survey, cross-sectional study, and model testing using structural equation modeling. SETTING: Two inpatient and outpatient SCI rehabilitation units, Sheba Medical Center and Loewenstein Hospital, Israel. PARTICIPANTS: Convenience sample of 156 individuals with SCI (N=156). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: QoL assessed by the World Health Organization Quality of Life Assessment-BREF. Neurological impairment after SCI reflected by lesion completeness and neurologic level of injury as measured by the International Standards for Neurological Classification of Spinal Cord Injury. The Spinal Cord Independence Measure to assess SCI-related task performance. ICF Brief Core Sets composition scores to assess impairment in body structure and function domains, limitations in activities, restriction in participation constructs, and the effect of environmental factors within the ICF model. RESULTS: Level of spinal cord injury and ICF Brief Core Sets composite score relating to activities and participation construct demonstrated a direct significant association with QoL. Moreover, a significant indirect association with QoL was found between the composite scores in ICF body structure and function and environmental factors, level of spinal cord injury, time since injury onset, and sex. Because the Spinal Cord Independence Measure was not related to QoL, we inferred that the categories related to instrumental activities of daily living and participation exert the most significant influence on QoL. CONCLUSIONS: In order to optimize improvements in quality of life, current rehabilitation programs should target limitations specifically related to instrumental activities of daily living and participation restrictions. It may serve as a focal point for further development of current therapeutic models and analytical methods that optimize rehabilitation planning and decision making among both health care professionals and patients.

Differences in sensorimotor and functional recovery between the dominant and non-dominant upper extremity following cervical spinal cord injury.

STUDY DESIGN: Post hoc analysis of prospective multi-national, multi-centre cohort study. OBJECTIVE: Determine whether cerebral dominance influences upper extremity recovery following cervical spinal cord injury (SCI). SETTING: A multi-national subset of the longitudinal GRASSP dataset (n = 127). METHODS: Secondary analysis of prospective, longitudinal multicenter study of individuals with cervical SCI (n = 73). Study participants were followed for up to 12 months after a cervical SCI, and the following outcome measures were serially assessed - the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) and the International Standards for the Neurological Classification of SCI (ISNCSCI), including upper extremity motor and sensory scores. Observed recovery and relative (percent) recovery were then determined for both the GRASSP and ISNCSCI, based on change from initial to last available assessment. RESULTS: With the exception of prehension performance (quantitative grasping) following complete cervical SCI, there were no significant differences (p < 0.05) for observed and relative (percent) recovery, between the dominant and non-dominant upper extremities, as measured using GRASSP subtests, ISNCSCI motor scores and ISNCSCI sensory scores. CONCLUSION: Despite well documented differences between the cerebral hemispheres, cerebral dominance appears to play a limited role in upper extremity recovery following acute cervical SCI.

Potential Role of Insulin-Like Growth Factors in Myofascial Pain Syndrome: A Narrative Review.

ABSTRACT: Insulin-like growth factors have diverse functions in skeletal muscles by acting through multiple signaling pathways, including growth regulation and differentiation, anti-inflammation, and antioxidation. Insulin-like growth factors have anti-inflammatory effects and also play roles in nociceptive pathways, determining pain sensitivity, in addition to their protective role against ischemic injury in both the nervous system and skeletal muscle. In skeletal muscle, insulin-like growth factors maintain homeostasis, playing key roles in maintenance, accelerating muscle regeneration, and repair processes. As part of their maintenance role, increased levels of insulin-like growth factors may be required for the repair mechanisms after exercise. Although the role of insulin-like growth factors in myofascial pain syndrome is not completely understood, there is evidence from a recent study that insulin-like growth factor 2 levels in patients with myofascial pain syndrome are lower than those of healthy individuals and are associated with increased levels of inflammatory biomarkers. Importantly, higher insulin-like growth factor 2 levels are associated with increased pain severity in myofascial pain syndrome patients. This may suggest that too low or high insulin-like growth factor levels may contribute to musculoskeletal disorder process, whereas a midrange levels may optimize healing without contributing to pain hypersensitivity. Future studies are required to address the mechanisms of insulin-like growth factor 2 in myofascial pain syndrome and the optimal level as a therapeutic agent.

From acute to long-term alterations in pain processing and modulation after spinal cord injury: mechanisms related to chronification of central neuropathic pain.

ABSTRACT: A severe and debilitating consequence of a spinal cord injury (SCI) is central neuropathic pain (CNP). Our aim was to investigate the processes leading to CNP emergence and chronification by analyzing causal relationship over time between spinothalamic function, pain excitability, and pain inhibition after SCI. This longitudinal follow-up study included 53 patients with acute SCI and 20 healthy controls. Spinothalamic, pain excitability, and intrasegmental and extrasegmental pain inhibition indices were repeatedly evaluated at 1.5, 3, and 6 months post-SCI. Between- and within-group analyses were conducted among those patients who eventually developed CNP and those who did not. Healthy controls were evaluated twice for repeatability analysis. Patients who developed CNP, compared with those who did not, exhibited increased thermal thresholds (P < 0.05), reduced pain adaptation (P < 0.01), and conditioned pain modulation (P < 0.05), early post-injury, and the CNP group's manifestations remained worse throughout the follow-up. By contrast, allodynia frequency was initially similar across SCI groups, but gradually increased in the subacute phase onward only among the CNP group (P < 0.001), along with CNP emergence. Early worse spinothalamic and pain inhibition preceded CNP and predicted its occurrence, and early worse pain inhibition mediated the link between spinothalamic function and CNP. Crossover associations were observed between early and late pain inhibition and excitability. Inefficient intrasegmental and extrasegmental inhibition, possibly resulting from spinothalamic deafferentation, seems to ignite CNP chronification. Pain excitability probably contributes to CNP maintenance, possibly via further exhaustion of the inhibitory control. Preemptive treatment promoting antinociception early post-SCI may mitigate or prevent CNP.

Functional outcomes following inpatient rehabilitation of Guillain-Barré syndrome patients: Intravenous immunoglobulins versus plasma exchange.

BACKGROUND: Treatment with either Intravenous immunoglobulin (IVIg) or plasma exchange (PE) in patients with Guillain-Barré Syndrome (GBS) showed equivalent efficacy as attested by a commonly used disability scale. However, it has been suggested that this scale may not be sensitive enough to detect subtle functional changes between the two treatments since it mainly focuses on walking capability and respiratory function. OBJECTIVE: To evaluate functional outcomes following treatment with IVIg or PE using comprehensive scales that incorporate parameters of basic activities of daily living. METHODS: A retrospective cohort study was conducted between 2007 and 2013 in an inpatient neurologic rehabilitation department. The study group included 70 individuals with GBS: 39 were treated with PE and 31 with IVIg. A comparison of functional outcomes was performed using Functional Independence Measure (FIM), rehabilitation efficiency (REy), rehabilitation effectiveness (REs), and the GBS disability scale (GDS). RESULTS: Both treatments had a comparable effect on the various functional outcomes. Patients showed a significant increase in total FIM scores (30 points on average) during rehabilitation mainly as a result of an increase in motor sub-scores. A mean improvement of 1.23 (SD 0.9) in GDS was also observed. On average, individuals with GBS spent 20 days combined in the acute departments and 61 days in the rehabilitation department, with length of stay being similar for both treatments. CONCLUSIONS: IVIg and PE treatments have similar basic activities of daily living (ADL) functional outcomes. Nevertheless, due to the different mechanism of actions of these treatments and the multitude of GBS variants, it is possible that further comprehensive assessment tools may demonstrate differences in activity and participation of individuals with GBS.

Early Trauma Predictors of Mobility in People with Spinal Cord Injury.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: This study aims to assess the potential value of very early trauma variables such as Abbreviated Injury Scale (AIS) and the Injury Severity Score for predicting independent ambulation following a traumatic spinal cord injury (TSCI). SUMMARY OF BACKGROUND DATA: Several models for prediction of ambulation early after TSCI have been published and validated. The vast majority rely on the initial examination of American Spinal Injury Association (ASIA) impairment scale and level of injury; however, in many locations and clinical situations this examination is not feasible early after the injury. METHODS: Patient characteristics, trauma data, and ASIA scores on admission to rehabilitation were collected for each of the 144 individuals in the study. Outcome measure was the indoor mobility item of the Spinal Cord Independence Measure taken upon discharge from rehabilitation. Univariate and multivariable models were created for each predictor, Odds ratios (ORs) were obtained by a multivariable logistic regression analysis, and area under the receiver operator curve was calculated for each model. RESULTS: We observed a significant correlation between the trauma variables and independent ambulation upon discharge from rehabilitation. Of the early variables, the AIS for the spine region showed the strongest correlation. CONCLUSION: These findings support using preliminary trauma variables for early prognostication of ambulation following a TSCI, allowing for tailored individual interventions.Level of Evidence: 3.

Performance in complex life situations: effects of age, cognition, and walking speed in virtual versus real life environments.

BACKGROUND: Virtual reality (VR) enables objective and accurate measurement of behavior in ecologically valid and safe environments, while controlling the delivery of stimuli and maintaining standardized measurement protocols. Despite this potential, studies that compare virtual and real-world performance of complex daily activities are scarce. This study aimed to compare cognitive strategies and gait characteristics of young and older healthy adults as they engaged in a complex task while navigating in a real shopping mall and a high-fidelity virtual replica of the mall. METHODS: Seventeen older adults (mean (SD) age = 71.2 (5.6) years, 64% males) and 17 young adults (26.7 (3.7) years, 35% males) participated. In two separate sessions they performed the Multiple Errands Test (MET) in a real-world mall or the Virtual MET (VMET) in the virtual environment. The real-world environment was a small shopping area and the virtual environment was created within the CAREN™ (Computer Assisted Rehabilitation Environment) Integrated Reality System. The performance of the task was assessed using motor and physiological measures (gait parameters and heart rate), MET or VMET time and score, and navigation efficiency (cognitive performance and strategy). Between (age groups) and within (environment) differences were analyzed with ANOVA repeated measures. RESULTS: There were no significant age effects for any of the gait parameters but there were significant environment effects such that both age groups walked faster (F(1,32) = 154.96, p < 0.0001) with higher step lengths (F(1,32) = 86.36, p < 0.0001), had lower spatial and temporal gait variability (F(1,32) = 95.71-36.06, p < 0.0001) and lower heart rate (F(1,32) = 13.40, p < 0.01) in the real-world. There were significant age effects for MET/VMET scores (F(1,32) = 19.77, p < 0.0001) and total time (F(1,32) = 11.74, p < 0.05) indicating better performance of the younger group, and a significant environment effect for navigation efficiency (F(1,32) = 7.6, p < 0.01) that was more efficient in the virtual environment. CONCLUSIONS: This comprehensive, ecological approach in the measurement of performance during tasks reminiscent of complex life situations showed the strengths of using virtual environments in assessing cognitive aspects and limitations of assessing motor aspects of performance. Difficulties by older adults were apparent mainly in the cognitive aspects indicating a need to evaluate them during complex task performance.

Split-arm swinging: the effect of arm swinging manipulation on interlimb coordination during walking.

Human locomotion is defined by bilateral coordination of gait (BCG) and shared features with the fore-hindlimb coordination of quadrupeds. The objective of the present study is to explore the influence of arm swinging (AS) on BCG. Sixteen young, healthy individuals (eight women; eight right motor-dominant, eight left-motor dominant) participated. Participants performed 10 walking trials (2 min). In each of the trials AS was unilaterally manipulated (e.g., arm restriction, weight on the wrist), bilaterally manipulated, or not manipulated. The order of trials was random. Walking trials were performed on a treadmill. Gait kinematics were recorded by a motion capture system. Using feedback-controlled belt speed allowed the participants to walk at a self-determined gait speed. Effects of the manipulations were assessed by AS amplitudes and the phase coordination index (PCI), which quantifies the left-right anti-phased stepping pattern. Most of the AS manipulations caused an increase in PCI values (i.e., reduced lower limb coordination). Unilateral AS manipulation had a reciprocal effect on the AS amplitude of the other arm such that, for example, over-swinging of the right arm led to a decrease in the AS amplitude of the left arm. Side of motor dominance was not found to have a significant impact on PCI and AS amplitude. The present findings suggest that lower limb BCG is markedly influenced by the rhythmic AS during walking. It may thus be important for gait rehabilitation programs targeting BCG to take AS into account.NEW & NOTEWORTHY Control mechanisms for four-limb coordination in human locomotion are not fully known. To study the influence of arm swinging (AS) on bilateral coordination of the lower limbs during walking, we introduced a split-AS paradigm in young, healthy adults. AS manipulations caused deterioration in the anti-phased stepping pattern and impacted the AS amplitudes for the contralateral arm, suggesting that lower limb coordination is markedly influenced by the rhythmic AS during walking.

Predicting the Risk for Central Pain Using the Sensory Components of the International Standards for Neurological Classification of Spinal Cord Injury.

Central neuropathic pain (CP) after spinal cord injury (SCI) is excruciating and difficult to manage. Pre-emptive treatment could be initiated in patients at risk for CP providing that it can be predicted. A combination of psychophysical tests could predict CP, but the process necessitates sophisticated equipment and constant monitoring. A simple predictive tool for CP is required. The aim of this study was to test the predictability for CP of the sensory component of the International Standards for Neurological Classification of Spinal Cord Injury (SC-ISNCSCI), routinely performed on all SCI patients. In an historical-prospective study, the SC-ISNCSCI and background variables were extracted from medical records of 115 SCI patients. In a prospective study, 20 SCI patients underwent the SC-ISNCSCI at admission and were followed-up for 12 months. In both studies, pinprick (PP) and light touch (LT) scores from the SC-ISNCSCI and the difference between them (LT-PP) were compared between those who eventually developed CP and those who did not. Heat-pain and touch thresholds were measured and correlated with the SC-ISNCSCI to test its validity. In both studies, patients who developed CP had, prior to CP, lower PP than LT scores, and lower PP scores than those who did not develop CP. At-level delta LT-PP score>1 best predicted CP; the odds of developing CP with LT-PP>1 was 24.4 times that of the reverse category (LT-PP<1). Heat-pain and touch thresholds significantly correlated with PP and LT. We conclude that the SC-ISNCSCI can be used as a clinical biomarker of CP with high probability.

Self-selected gait speed--over ground versus self-paced treadmill walking, a solution for a paradox.

BACKGROUND: The study of gait at self-selected speed is important. Traditional gait laboratories being relatively limited in space provide insufficient path length, while treadmill (TM) walking compromises natural gait by imposing speed variables. Self-paced (SP) walking can be realized on TM using feedback-controlled belt speed. We compared over ground walking vs. SP TM in two self-selected gait speed experiments: without visual flow, and while subjects were immersed in a virtual reality (VR) environment inducing natural visual flow. METHODS: Young healthy subjects walked 96 meters at self-selected comfortable speed, first over ground and then on the SP TM without (n=15), and with VR visual flow (n=11). Gait speed was compared across conditions for four 10 m long segments (7.5 - 17.5, 30.5 - 40.5, 55.5 - 65.5 and 78.5-88.5 m). RESULTS: During over ground walking mean (± SD) gait speed was equal for both experimental groups (1.50 ± 0.13 m/s). Without visual flow, gait speed over SP TM was smaller in the first and second epochs as compared to over ground (first: 1.15 ±0.18 vs. second: 1.53 ± 0.13 m/s; p<0.05), and was comparable in the third and fourth (1.45 ± 0.19 vs. 1.49 ± 0.15 m/s; p>0.3). With visual flow, gait speed became comparable to that of over ground performance already in the first epoch (1.43 ± 0.22 m/s; p>0.17). Curve fitting analyses estimated that steady state velocity in SP TM walking is reached after shorter distanced passed with visual flow (24.6 ± 14.7 m) versus without (36.5 ± 18.7 m, not statistically significant; p=0.097). Steady state velocity was estimated to be higher in the presence of visual flow (1.61 ± 0.17 m/s) versus its absence (1.42 ± 1.19 m/s; p<0.05). CONCLUSIONS: The SP TM walking is a reliable method for recording typical self-selected gait speed, provided that sufficient distance is first passed for reaching steady state. Seemingly, in the presence of VR visual flow, steady state of gait speed is reached faster. We propose that the gait research community joins forces to standardize the use of SP TMs, e.g., by unifying protocols or gathering normative data.

Improving the diagnostic accuracy of ultrasonography in suspected acute appendicitis by the combined transabdominal and transvaginal approach.

Transabdominal ultrasound has a lower diagnostic yield in acute appendicitis than computed tomography (CT) scanning. The addition of transvaginal sonography in women with suspected appendicitis has shown improvement in the efficacy of diagnosis, potentially providing the option of selective CT use and reducing overall investigative cost and surgical delay. Two hundred ninety-two women who underwent combined transabdominal and transvaginal ultrasound for suspected acute appendicitis were evaluated. Patients were divided into two groups; Group 1 including patients with a positive sonographic diagnosis of appendicitis who underwent operation and Group 2 including patients with a negative sonographic diagnosis. Of the 157 women in Group 1, the diagnosis of appendicitis was histologically confirmed in 144 patients with five cases having a normal appendix in whom eight other pathologies were found. Of the 135 women with negative ultrasound examinations, 14 underwent surgery in which four cases of appendicitis were found. The sensitivity of the combined approach was 97.3 per cent, the specificity 91 per cent, the positive predictive value 91.7 per cent, and the negative predictive value 97 per cent. Combined ultrasound has a high predictive value for the diagnosis of appendicitis and may assist in reduction of the use of CT scanning for diagnosis and in the negative appendectomy rate.