The Impact of Light Touch and Pin Prick on Functional Outcomes in Patients with Traumatic Spinal Cord Injury.

A spinal cord injury (SCI) can cause severe lifelong functional disability and profoundly affect an individual's daily life. We investigated the prediction of patients' post-SCI functional outcomes by evaluating sensory scores rather than motor scores, as the latter's association with functional outcomes is well established. We examined patients' responses to a light touch (LT) and pin prick (PP) at admission and the response data's usefulness as predictors of functional outcomes (i.e., ability to perform activities of daily living) at discharge. This exploratory observational study used data from the Japanese National Spinal Cord Injury Database (SCI-J). Data from 3,676 patients who met the inclusion criteria and were admitted for an SCI between 1997 and 2020 were analyzed. The motor score of the Functional Independence Measure (mFIM) at discharge was used as an index of functional outcome. A multiple regression analysis revealed that the mFIM was associated with both the LT response (ß=0.07 (0.01), p<0.001) and the PP response (ß=0.07 (0.01), p<0.001) at admission. The false discovery rate log-worth values for LT and PP were 6.6 and 8.5, respectively. Our findings demonstrate that LT and PP scores at admission can help predict patients' functional outcomes after an SCI, although the magnitude of their contributions is not high.

Increase in Serum Interleukin-1 Receptor Antagonist (IL-1ra) Levels after Wheelchair Half Marathon Race in Male Athletes with Spinal Cord Injury.

Exercise increases the serum level of interleukin-6 (IL-6), which in turn stimulates the production of various inflammatory cytokine antagonists, such as interleukin-1 receptor antagonist (IL-1ra). Individuals with cervical spinal cord injury (CSCI) are at high risk of inflammatory conditions. This study compared the effects of wheelchair half marathon on the immune system of male athletes with CSCI and those with thoracic/lumber spinal cord injury (SCI). Neutrophil count, IL-1ra, IL-6, and various endocrine parameters were measured before, immediately and 1 h after the race in five CSCI and six SCI who completed the wheelchair marathon race. The percentage of neutrophils was significantly higher in CSCI immediately and 1 h after the race, compared with the baseline, and significantly higher in SCI at 1 h after the race. IL-6 was significantly higher immediately and 1 h after the race in SCI, whereas no such changes were noted in IL-6 in CSCI. IL-1ra was significantly higher at 1 h after the race in both SCI and CSCI. The race was associated with an increase in IL-1ra in both CSCI and SCI. These findings suggest wheelchair half marathon race increases IL-1ra even under stable IL-6 status in male CSCI individuals, and that such post-race increase in IL-1ra is probably mediated through circulatory neutrophils.

Long-Term Safety and Efficacy of Mirogabalin for Central Neuropathic Pain: A Multinational, Phase 3, 52-Week, Open-Label Study in Asia.

INTRODUCTION: Central neuropathic pain (CNeP) is difficult to treat and has diverse etiology, including spinal cord injury (CNePSCI), Parkinson's disease (CNePPD), and central post-stroke pain (CPSP). The safety and efficacy of mirogabalin have been demonstrated in short-term trials, including patients with CNePSCI. The objective of our study was to confirm the safety/efficacy of mirogabalin in patients with CNePPD and CPSP, and obtain long-term data for CNePSCI. METHODS: This 52-week, open-label extension of a previous randomized controlled study was conducted across Japan, Korea, and Taiwan. Patients with CNePSCI, CNePPD, or CPSP received twice daily (BID) 5-10 mg mirogabalin for a 4-week titration period, after which the dosage was maintained for 47 weeks at a maximum of 15 mg BID, followed by a 1-week taper period receiving the same dose but only administered once daily. The primary endpoint was safety, assessed primarily by incidence and severity of treatment-emergent adverse events (TEAEs). Efficacy was assessed in a post hoc analysis of data obtained by the short-form McGill Pain Questionnaire (SF-MPQ). RESULTS: Of the 210 patients enrolled, 106, 94, and 10 had CNePSCI, CPSP, and CNePPD, respectively. The mean overall age of patients was 62.9 years, and most patients were male and of Japanese ethnicity. TEAEs occurred in 84.8% of patients, the most common being somnolence (16.7%), peripheral edema (12.4%), edema (11.4%), nasopharyngitis (11.0%), and dizziness (7.6%). Most TEAEs were mild. Severe and serious TEAEs occurred in 6.2% and 13.3% of patients, respectively. All patient groups experienced reductions in SF-MPQ visual analog scores for pain: mean ± standard deviation changes from baseline at week 52 were -2.3 ± 21.13 mm (CNePSCI), -17.0 ± 24.99 mm (CPSP), and -17.1 ± 35.32 mm (CNePPD). CONCLUSION: Mirogabalin was generally safe, well tolerated, and effective for treatment of CNeP in this long-term study. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03901352.

Renal and Endocrine Responses to Arm Exercise in Persons with Cervical Spinal Cord Injury.

The aim of this study was to assess renal functions and endocrine responses to arm exercise in persons with cervical spinal cord injury (CSCI) under euhydrated conditions (free drinking of water), and to determine the physiological effects of exercise on renal function in these subjects. Eleven CSCI individuals (spinal lesions between C6 and C8, American Spinal Injury Association impairment scale A) and nine able-bodied (AB) persons rested for 30 min before performing 30 min arm-crank ergometer exercises at 50% of their maximum oxygen consumption, followed by 60-min of rest/recovery. Urine and blood samples were collected before and immediately after the exercise and recovery period. The CSCI patients showed no increase in plasma adrenaline and plasma renin activity compared with the AB controls, but showed similar changes in plasma aldosterone and the plasma antidiuretic hormone in response to the exercise. Creatinine clearance, osmolal clearance, free water clearance, and the fractional excretion of Na+ did not change during exercise in both groups of subjects, however free water clearance in the CSCI group was higher than in the AB group throughout the study. These findings suggested that activated plasma aldosterone without an increase in adrenaline or renin activity during exercise in CSCI individuals may reflect an adaptation to the disturbance of the sympathetic nervous system to compensate for renal function. As a result, no adverse effects of exercise on renal function in CSCI patients were observed.

Comparative analysis of effects of various toilet seat cushions on buttock pressure during toileting in persons with spinal cord injury.

OBJECTIVES: To measure buttock pressure during toilet seating in persons with spinal cord injury (SCI). DESIGN: A case series study. SETTING: Kibikogen Rehabilitation Center for Employment Injuries. METHODS: The study included 41 persons with SCI. Buttock pressure was measured during toilet seating, with or without a toilet seat cushion (foam cushion, gel cushion, air cushion) on the toilet seat. RESULTS: The subjects were classified into three groups according to the site of the maximum pressure [greater trochanter (GT) region, ischial tuberosities (IT), and sacral region (SR)] recorded on the pressure map of the non-cushioned toilet seat, into the GT, IT and SR groups, respectively. All three types of cushions altered the buttock pressure distribution during no-cushion toilet seating. In the GT group, all three cushions significantly reduced the peak pressure in the GT area, compared to the control (no-cushion). The foam cushion significantly increased the peak pressure in the IT area (Pisch) in the GT group, relative to the control. However, the foam cushion significantly increased while the gel cushion significantly reduced Pisch, relative to the control. In SR group, the air cushion significantly reduced the peak pressure in the SR, relative to the control. CONCLUSION: We recommend the use of the gel cushion for the IT group and the air cushion in GT and SR group to reduce buttock pressure during toilet seating in persons with SCI.

Mirogabalin for Central Neuropathic Pain After Spinal Cord Injury: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study in Asia.

BACKGROUND AND OBJECTIVES: Patients with spinal cord injury (SCI) commonly experience central neuropathic pain (CNeP), which is challenging to treat. Mirogabalin is effective for peripheral neuropathic pain, but evidence for CNeP is lacking. METHODS: This randomized, double-blind, placebo-controlled, phase 3 study investigated mirogabalin efficacy and safety for the treatment of CNeP in patients with traumatic SCI. Adult patients from 120 sites throughout Japan, Korea, and Taiwan were randomized (1:1) to receive placebo or mirogabalin (5 mg twice daily [BID] for 1 week, 10 mg BID for 1 week, and 10 or 15 mg BID for 12 weeks). Patients with moderate renal impairment received half the dosage. The primary efficacy endpoint was change from baseline in the weekly average daily pain score (ADPS) at week 14. The secondary endpoints included ADPS responder rates, the Short-Form McGill Pain Questionnaire (SF-MPQ), average daily sleep interference score (ADSIS), and Neuropathic Pain Symptom Inventory (NPSI). Adverse events were monitored for safety. RESULTS: Each treatment group comprised 150 patients. Mirogabalin elicited a statistical and clinically relevant improvement in change from baseline in the weekly ADPS at week 14 (least-squares mean difference [95% CI] vs placebo -0.71 [-1.08 to -0.34], p = 0.0001). Responder rates at week 14 were higher for mirogabalin than those for placebo (odds ratio [95% CI] 1.91 [1.11-3.27] for the ≥30% responder rate; 2.52 [1.11-5.71] for the ≥50% responder rate). Statistical improvements (i.e., least-squares mean difference [95% CI] vs placebo) were also observed in the SF-MPQ (-2.4 [-3.8 to -1.1]), ADSIS -0.71 (-1.04 to -0.38), and NPSI -7.7 (-11.1 to -4.4) scores. Most treatment-emergent adverse events were mild; no serious adverse drug reactions were reported. DISCUSSION: Mirogabalin elicited clinically relevant decreases in pain and was well tolerated, suggesting that mirogabalin is a promising treatment for patients with CNeP due to SCI. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov (NCT03901352); first submitted April 3, 2019; first patient enrolled March 14, 2019; available at clinicaltrials.gov/ct2/show/NCT03901352. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in adult patients with CNeP due to traumatic SCI, mirogabalin, 10 or 15 mg BID, effectively improves weekly ADPS at week 14.

Wheelchair marathon creates a systemic anti-inflammatory environment in persons with spinal cord injury.

OBJECTIVE: To investigate interleukin (IL)-6 and other inflammation markers in athletes with spinal cord injury (SCI) during a wheelchair marathon race. DESIGN: Nonrandomized study in an actual race. SETTING: The 28th Oita International Wheelchair Marathon Race, Japan. PARTICIPANTS: Twenty-eight men with SCI between T7 and L2 (16 full-marathon racers, full-group; and 12 half-marathon racers, half-group). MAIN OUTCOME MEASURES: Plasma IL-6, tumor necrosis factor (TNF)-α, and high-sensitivity C-reactive protein (hsCRP) were measured the day before, immediately after the race, and 2 hours after the race. RESULTS: Plasma IL-6 concentrations increased by 18.4-fold and by 9.4-fold (P < 0.05) in the full- and half-groups immediately after the race (P < 0.05), respectively, but returned to baseline at 2 hours of recovery. In contrast, plasma TNF-α and hsCRP did not change throughout the race in both groups. The fold change in plasma IL-6 immediately after the race relative to the prerace was significantly higher in the full-group than the half-group (P < 0.05). In both groups, plasma IL-6 immediately after the race did not correlate with the average wheelchair speed. Interestingly, plasma IL-6 and hsCRP before the race in the full-group, but not in half-group, correlated negatively with the average wheelchair speed (P < 0.05). CONCLUSIONS: The study demonstrated that half- and full-marathon wheelchair races increased plasma IL-6, but not TNF-α and hsCRP. Furthermore, the top athletes of the full-group had low plasma IL-6 and hsCRP at baseline. Wheelchair marathon competition, especially full-marathon, and daily training seem to have beneficial effects on SCI through the plasma IL-6 response.

Does 20-min arm crank ergometer exercise increase plasma interleukin-6 in individuals with cervical spinal cord injury?

Interleukin-6 (IL-6) is produced by contracting skeletal muscles and then released into the circulation and considered to mediate the health benefits of exercise against chronic diseases. Individuals with spinal cord injury (SCI) are reported to be at higher risk of developing metabolic diseases. We investigated the IL-6 responses to 20-min arm crank ergometer exercise at 60% of maximum oxygen consumption in eight trained individuals with cervical SCI (CSCI) between C6 and C7, and eight able-bodied trained healthy subjects. The plasma concentrations of IL-6, adrenaline, prostaglandin E(2) and cortisol were measured before, immediately after the exercise, 1 and 2 h after exercise. At rest, the plasma adrenaline concentration was significantly lower in individuals with CSCI than in able-bodied subjects (P < 0.01). On the other hand, the concentration of IL-6 was significantly higher at rest in individuals with CSCI (2.18 ± 0.44 pg/ml, mean ± SEM) than the control (1.02 ± 0.22 pg/ml, P < 0.05). In able-bodied subjects, the plasma adrenaline concentration increased significantly immediately after the exercise (P < 0.01) and returned to the baseline level at 1 h after exercise, and the plasma IL-6 level increased significantly at 1 h after exercise (1.91 ± 0.28 pg/ml, P < 0.05) and returned to the baseline level at 2 h after exercise. In contrast, adrenaline and IL-6 levels were steady throughout the study in individuals with CSCI. The lack of exercise-related IL-6 response in individuals with CSCI could be due to muscle atrophy and sympathetic nervous system dysfunction.

The effect of service dogs on the improvement of health-related quality of life.

To assess the effects of service dogs on health-related quality of life (HRQOL), we conducted a survey of 10 service dog owners using SF-36v2 (Medical Outcomes Study 36 Item Short-Form Health Survey Version 2.0) and compared it with a matched control group of people with physical disabilities who did not have service dogs but were eligible for one. The scores for mental health and role emotional of service dog owners were relatively high, and their mental component summary was higher than the general population norm. These results indicate that service dogs affect the mentality of their owners. The comparison with the control group indicated that service dogs alleviate the mental burden of daily activities, and subjectively improved the physical functioning of their owners. This study showed that service dogs have positive functional and mental effects on their disabled owners.

Autonomic dysreflexia during a bowel program in patients with cervical spinal cord injury.

The purpose of the present study was to investigate the relationship between bowel maneuvers and autonomic dysreflexia (AD) in patients with cervical spinal cord injuries (CSCI). Fifteen consecutive, clinically stable patients with CSCI participated. We evaluated changes in blood pressure (BP), pulse rate (PR) and classic symptoms of AD before, during and after a bowel program involving the manual removal of stool in lateral recumbency. The insertion of rectal medication induced a significant increase in systolic BP, which persisted during additional digital rectal stimulation. Furthermore, the manual removal of stool induced AD, with maximal increases of systolic BP (169.1(+-)19.5 mmHg, mean(+-)SD). However, the insertion of a finger into the anus after the end of stool flow did not cause a further increase in systolic BP. Systolic BP recovered to pre-program values within 5 min after defecation. Our study demonstrated that the combined effects of rectal and/or anal sphincter distension and uninhibited rectal contraction in response to the manual removal of stool might induce AD. We recommend avoiding, if at all possible, the manual removal of stool in order to prevent AD in patients with CSCI.

Activation of natural killer cell function in recreational athletes with paraplegia during a wheelchair half-marathon race.

OBJECTIVE: To investigate a part of the immune homeostasis in recreational athletes with spinal cord injury (SCI) during and after a wheelchair half-marathon race. DESIGN: Case-control study in an actual race. SETTING: The half-marathon division of an international wheelchair marathon race in Japan. PARTICIPANTS: Seven male wheelchair racers with SCI between T7 and L1. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Changes in the number and function of natural killer (NK) cells and the endocrine effects, including plasma catecholamines and cortisol in blood samples obtained the day before the race, immediately after it, and 1 day after the race. RESULTS: Both the percentage and absolute number of peripheral NK cells did not change significantly throughout the experiment. Mean NK cell cytotoxic activity +/- standard deviation increased significantly, from 45.5%+/-7.5% to 56.1%+/-5.1% (P<.01) immediately after the race and remained increased until the next day. Plasma adrenaline levels were increased (P<.05) immediately after the race and recovered 1 day later; the plasma concentration of cortisol did not change throughout the experiment. CONCLUSIONS: The wheelchair half-marathon race induced activation of NK cell function in recreational athletes with SCI between T7 and L1.

Cardiovascular and endocrine responses during the cold pressor test in subjects with cervical spinal cord injuries.

OBJECTIVE: To investigate cardiovascular regulation and endocrine responses during the cold pressor test in patients with chronic spinal cord injury (SCI). DESIGN: Experimental and control study. SETTING: University laboratory, department of rehabilitation medicine, in Japan. PARTICIPANTS: Eight quadriplegic subjects with complete spinal cord transection at the C6 to C8 level and 6 age-matched healthy subjects. INTERVENTIONS: Cardiovascular and endocrine responses were examined during 2 minutes of control, 3 minutes of ice-water immersion of the foot, followed by a 3-minute recovery. MAIN OUTCOME MEASURES: Blood pressure, heart rate, the Borg 15-point Rating of Perceived Pain Scale, and blood samples for measurement of plasma norepinephrine, epinephrine, plasma renin activity, plasma aldosterone, and arginine vasopressin. RESULTS: The rise in the mean arterial blood pressure during the cold pressor test in patients with SCI (baseline, 81.6+/-3.7mmHg; increased by 30%+/-6.1%) was significantly (P<.05) higher than that in healthy subjects (baseline, 101.2+/-4.5mmHg; increased by 20%+/-4.5%). The SCI subjects had no change in heart rate throughout the test, in contrast to the tachycardia noted in normal subjects. Baseline plasma norepinephrine in SCI subjects (63.0+/-18.3pg/mL) was significantly lower than in normal subjects (162.3+/-19.6pg/mL) and plasma norepinephrine increased significantly during the cold pressor test in both groups. CONCLUSIONS: In the SCI subjects, a reflex sympathetic discharge through the isolated spinal cord results in a more profound rise in mean blood pressure during ice-water immersion. This response was free of inhibitory impulses from supraspinal center and baroreceptor reflexes, either of which might restrain the increase in blood pressure.