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Study design: Acute experimental study. Objectives: Cold-induced vasodilation is a local mechanism of protection against frostbite in non-injured persons. We assessed whether an increase in skin blood flow (SkBF) during local cooling (LC) was observed in individuals with spinal cord injuries (SCIs) and if the response patterns differed between region levels or sites. Setting: Laboratory of Wakayama Medical University and the affiliated clinics, Japan. Methods: A local cooler device (diameter 4 cm) was placed on the chest (sensate) and right thigh (non-sensate) in persons with cervical (SCIC; n= 9) and thoracolumbar SCIs (SCITL; n= 9). After the surface temperature under the device was controlled at 33 °C for 10 min (baseline), LC (−0.045 °C/s) was applied and the skin temperature was maintained at 15 and 8 °C for 15 min of each stage. SkBF (laser Doppler flowmetry) was monitored using a 1-mm needle-type probe inserted into its center. Results: The percent change in SkBF (%ΔSkBF) on the chest remained unchanged until the end of 15 °C stage; thereafter, it increased to a level at least 70% greater than the baseline during the 8 °C stage in both groups. The %ΔSkBF on the thigh in both SCICand SCITLnotably increased from 8 and 6 min respectively, during the 8°C stage, compared to 1 min before the stage; however, it did not exceed the baseline level. Conclusions: An increase in SkBF during LC was observed both in the sensate and non-sensate areas in SCIs, although the magnitude was larger in the sensate area.

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.

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.

Study design: Experimental study. Objectives: To compare lipid profiles during moderate-intensity exercise between persons with cervical spinal cord injuries (SCIC) and able-bodied controls (AB). Setting: Wakayama Medical University, Japan. Methods: Six participants with SCICand six AB performed 30-min arm-crank exercise at 50% VO2peak. Blood samples were collected before (PRE), immediately (POST), and 60 min after exercise (REC). Concentrations of serum free fatty acids ([FFA]s), total ketone bodies ([tKB]s), acetoacetic acid ([AcAc]s), insulin ([Ins]s), and plasma catecholamines and glucose ([Glc]p) were assessed. Results: Catecholamine concentrations in SCICwere lower than AB throughout the experiment (P< 0.001) and remained unchanged, while increased at POST in AB (P< 0.01). [FFA]sremained unchanged in both groups with no differences between groups. [tKB]sin SCICtended to increase at REC from PRE (P= 0.043), while remaining unchanged in AB (P> 0.42). [AcAc]sin SCICincreased at REC from PRE and POST (P< 0.01) while remaining unchanged in AB (interactions of Group × Time P= 0.014). [Glc]pand [Ins]swere comparable between the groups throughout the study. Conclusion: Serum ketone bodies in SCICincreased after exercise while remaining unchanged in AB, suggesting that suppressed uptakes of serum ketone bodies from blood to the muscles in SCICwould partially contribute the increased serum ketones.

ContextIndonesia, Japan, Korea, Thailand.ObjectiveTo culturally validate and translate the Scientific Exercise Guidelines for Adults with Spinal Cord Injury (SEG-SCI) for use in four Asian countries.DesignSystematic ReviewParticipantsN/AMethodsA systematic review was conducted to identify all published English- and local-language studies conducted in Indonesia, Japan, Korea, and Thailand, testing the effects of exercise training interventions on fitness and cardiometabolic health in adults with acute or chronic SCI. Protocols and results from high-quality controlled studies were compared with the SEG-SCI. Forward and backward translation processes were used to translate the guidelines into Bahasa Indonesian, Japanese, Korean and Thai languages.ResultsFifteen studies met the review criteria. At least one study from each country implemented exercise prescriptions that met or exceeded the SEG-SCI. Two were controlled studies. In those two studies, relative to control conditions, participants in exercise conditions achieved significant improvements in fitness or cardiometabolic health outcomes only when the exercise intervention protocol met or exceeded the SEG-SCI. During the language translation processes, end-users confirmed that SEG-SCI language and terminology were clear.ConclusionClinical researchers in Indonesia, Japan, Korea and Thailand have implemented exercise protocols that meet or exceed the SCI-SEG. Results of high-quality studies align with the SEG-SCI recommendations. Based on this evidence, we recommend that the SEG-SCI be adopted in these countries. The cultural validation and translation of the SEG-SCI is an important step towards establishing consistent SCI exercise prescriptions in research, clinical and community settings around the world.

Study design: Experimental study. Objectives: To compare lipid metabolism in individuals with a cervical spinal cord injury (SCIC) and able-bodied (AB) persons in response to mild cold stress. Settings: Laboratory of Wakayama Medical University, Japan. Methods: Nine males with SCICand 11 AB wore a water-perfusion suit in a supine position. Following 30-min rest thermoneutrality, the whole body was cooled by perfusing 25 °C water through the suit for 15–20 min (CS). Blood samples were collected before, immediately, and 60 (post-CS60) and 120 min after CS (post-CS120). Concentrations of serum free fatty acid ([FFA]s), total ketone bodies ([tKB]s), insulin ([Ins]s) and plasma adrenaline ([Ad]p), noradrenaline ([NA]p) and glucose ([Glc]p) were assessed. Results: [Ad]pin SCICwere lower than AB throughout the study (p= 0.0002) and remained largely unchanged in both groups. [NA]pincreased after cold stress in AB only (p< 0.0001; GxT p= 0.006). [FFA]sincreased by 62% immediately after cold stress in SCIC(p= 0.0028), without a difference between groups (p= 0.65). [tKB]sincreased by 69% at post-CS60 and 132% at post-CS120 from the start in SCICwith no differences between groups (p= 0.54). [Glc]pand [Ins]swere reduced in SCIc only (GxT p= 0.003 and p= 0.001, respectively). Conclusion: These data indicate that mild cold stress acutely elevates lipid and ketone body metabolism in persons with SCIc, despite the presence of sympathetic dysfunction.

Background We hypothesized that 3 weeks of preoperative rehabilitation could improve postoperative pain in patients undergoing total knee arthroplasty (TKA). Aim: This study aimed to evaluate the effects of 3 weeks of preoperative rehabilitation on postoperative pain after TKA.Methods This prospective cohort study included 29 subjects (41 knees) divided into two groups: the preoperative rehabilitation group included 14 subjects (20 knees) and the control group included 15 subjects (21 knees). All subjects were scheduled for unilateral or bilateral TKA. The preoperative rehabilitation group completed a 90-min rehabilitation program 3 days per week for 3 weeks before their TKA. The rehabilitation included body weight exercise, resistance exercise, and cycle ergometer exercise. The control group did not undergo any rehabilitation prior to TKA. We assessed the patients using Western Ontario and McMaster Universities’ Osteoarthritis Index (WOMAC) and recorded their physical activity of walking, standing, sitting, and lying down at study entry and/or before TKA and 1 month after TKA.Results The WOMAC total and WOMAC pain scores were significantly lower after 3-weeks of rehabilitation, but before TKA and 1 month after surgery were significantly lower in the preoperative rehabilitation group than in the control group. The time spent walking, standing, sitting, and lying down for 12 h did not change after TKA in the preoperative rehabilitation group. In contrast, in the control group, the time spent in walking and standing positions decreased and the time in the sitting position increased after TKA (p < 0.05). Conclusion: We found that 3-week preoperative training reduced knee pain and helped maintain physical activity after surgery in patients with severe osteoarthritis who underwent TKA.

Objective:Brain-derived neurotrophic factor (BDNF) has beneficial effects on metabolism as well as the peripheral and central nervous systems. The aim of this study was to assess the response of serum BDNF concentration ([BDNF]s) to wheelchair half marathon race in individuals with spinal cord injury (SCI).Design:Prospective observational study.Setting:The 34th Oita International Wheelchair Marathon Race in Japan.Participants:Nine cervical SCIs (CSCI) and 8 thoracic and lumber SCIs (LSCI) male athletes. Interventions:Wheelchair half-Marathon Race.Outcome measures:[BDNF]s, plasma concentrations of adrenaline ([Ad]p), noradrenaline ([Nor]p), and cortisol ([Cor]p), hematocrit, and platelet count were measured the day before, immediately after, and an hour after the race.Results:[BDNF]s increased significantly immediately after the race in both groups (CSCI; P = 0.0055, LSCI; P = 0.0312) but returned to the baseline levels at one hour after the race. However, [BDNF]s immediately and one hour after the race were significantly higher in LSCI than in CSCI (immediately after the race; P = 0.0037, 1 h after the race; P = 0.0206). Hematocrit and platelet count remained unchanged throughout the study. In LSCI, [Ad]p, [Nor]p and [Cor]p increased significantly immediately after and one hour after the race, compared with the baseline values (P < 0.05). On the other hand, these variables remained unchanged throughout the study in the CSCI.Conclusions:[BDNF]sincreased significantly from the baseline in both LCSI and CSCI but was higher in LSCI than in CSCI immediately after and one hour after the race.

Objective:To determine the relationship between physical findings, wheelchair sitting time, and interface pressure on ischial region in subjects with spinal cord injury (SCI).Design:Cross-sectional study.Setting:Rehabilitation center in Japan.Participants:Manual wheelchair users with chronic SCI (n = 45).Interventions:Pressure ulcers (PU) were diagnosed by inspection, palpation, and ultrasonography. Self-reports were obtained on wheelchair sitting time and pressure mapping was recorded while the subject was seated on the wheelchair.Outcome measures:Subjects were divided into those with ultrasonographically low-echoic lesions (PU-positive group, n = 11) and no such lesions (PU-negative group, n = 34). Outcome measures included wheelchair sitting time and interface pressure at bilateral ischial regions.Results:Using ultrasonography, 13 low-echoic lesions were identified in 11 subjects of the PU-positive group. The pressure duration was longer and interface pressure was significantly higher in subjects of the PU-positive group compared with those of the PU-negative group (P < 0.05 and P < 0.001, respectively).Conclusions:This is the first study to evaluate the interrelationship between physical findings, sitting time, and ultrasonographically measured interface pressure on ischial region area in subjects with spinal cord injury. To prevent pressure ulcers, we recommend avoidance of prolonged wheelchair sitting and measures that can reduce the interface pressure. These variables should be carefully tailored to the needs of the individual subjects with SCI.

Study design: Acute experimental study. Objectives: To investigate the acute response of markers of lipid metabolism and interleukin (IL)-6 to dopamine infusion in people with a cervical spinal cord injury (CSCI). Setting: Laboratory of Wakayama Medical University, Japan. Methods: Ten participants, four with CSCI and six AB individuals, underwent 50 min of dopamine infusion. Blood samples were collected prior to, immediately after and 1 h following cessation of dopamine infusion for the determination of circulating catecholamine, lipid, ketone body and IL-6 concentrations. Results: The adrenaline concentration following dopamine infusion was increased by 59 ± 7% in CSCI (p= 0.038, Cohen’s d effect size (ES): 1.47), while this was not changed in AB (p= 0.223). Triglycerides and acetoacetic acid concentration were increased in both groups, immediately after and 1 h post-infusion (triglycerides p≤ 0.042, ES CSCI: 1.00, ES AB: 1.12; acetoacetic acid p≤ 0.030; ES CSCI: 1.72, ES AB: 1.31). 3-Hydroxybutyric acid concentration was increased in CSCI only (48 ± 15%, p= 0.039, ES: 1.44; AB p= 0.115). Dopamine infusion did not affect plasma IL-6 concentration in either group (p≥ 0.368). Conclusions: Dopamine infusion induced a sustained increase in triglyceride and ketone body concentrations in persons with CSCI. In contrast, cytokine concentrations were not affected by dopamine infusion. These findings suggest that circulating catecholamines can stimulate metabolism in people with CSCI despite the presence of autonomic dysfunction.

Study design:Retrospective study.Objectives:To determine the best time to introduce non-invasive ventilation (NIV), clinical effectiveness of NIV, and complications of long-term use of NIV in patients with high-level cervical spinal cord injuries (CSCI).Setting:Public Hospital, Japan.Methods:The subjects were 14 tracheostomy ventilator-dependent patients, with above C3 spinal lesions, and American Spinal Cord Injury Association Impairment Scale A (ASIA A). They were referred to our clinic between 2005 and 2010 for switching mechanical ventilation support system from tracheostomy ventilation to NIV. Respiratory function tests were measured before and after NIV. Patients who were successfully switched to NIV were interviewed two years later and asked about their health and social status.Results:Eleven patients were successfully switched to NIV. The success rate of switching to NIV within 1 year was also high (P < 0.05). NIV improved the vital capacity of C2 ASIA A and C1 ASIA A patients with adequate respiratory accessory muscle strength sufficient to expand the chest wall. The time on ventilator-free spontaneous breathing increased or did not deteriorate after NIV. Three C1 ASIA A patients with insufficient muscle strength to expand the thorax mastered glossopharyngeal breathing and enjoyed a short ventilator-free time. All patients who were successfully switched to NIV lived in the community. Two patients developed minor complications after discharge and two died later for unrelated causes.Conclusion:Ventilator-dependent patients should be switched to NIV within 1 year of injury. Long-term NIV can improve respiratory function and clinical outcome.

Study design: Experimental study. Objective: Individuals with spinal cord injuries (SCI) may present with impaired sympathetic control over thermoregulatory responses to environmental and exercise stressors, which can impact regional core temperature (Tcore) measurement. The purpose of this study was to investigate whether regional differences in Tcoreresponses exist during exercise in individuals with SCI. Setting: Rehabilitation centre in Wakayama, Japan. Methods: We recruited 12 men with motor-complete SCI (7 tetraplegia, 5 paraplegia) and 5 able-bodied controls to complete a 30-min bout of arm-cycling exercise at 50% V̇O2peak reserve. Tcorewas estimated using telemetric pills (intestinal temperature; Tint) and esophageal probes (Teso). Heat storage was calculated from baseline to 15 and 30 min of exercise. Results: At 15 min of exercise, elevations in Teso(Δ0.39 ± 0.22 °C; P&lt; 0.05), but not Tint(Δ0.04 ± 0.18 °C; P= 0.09), were observed in able-bodied men. At 30 min of exercise, men with paraplegia and able-bodied men both exhibited increases in Teso(paraplegia: Δ0.56 ± 0.30 °C, P&lt; 0.05; able-bodied men: Δ0.60 ± 0.31 °C, P&lt; 0.05) and Tint(paraplegia: Δ0.38 ± 0.33 °C, P&lt; 0.05; able-bodied men: Δ0.30 ± 0.30 °C, P&lt; 0.05). Tesobegan rising 7.2 min earlier than Tint(pooled, P&lt; 0.01). Heat storage estimated by Tesowas greater than heat storage estimated by Tintat 15 min (P= 0.02) and 30 min (P= 0.03) in men with paraplegia. No elevations in Teso, Tint, or heat storage were observed in men with tetraplegia. Conclusions: While not interchangeable, both Tesoand Tintare sensitive to elevations in Tcoreduring arm-cycling exercise in men with paraplegia, although Tesomay have superior sensitivity to capture temperature information earlier during exercise.

Experimental study. To characterize static and dynamic cerebral autoregulation (CA) of individuals with cervical spinal cord injury (SCI) compared to able-bodied controls in response to moderate increases in mean arterial pressure (MAP) caused by mild whole-body cold stress. Japan Five men with complete autonomic cervical SCI (sustained > 5 y) and six age-matched able-bodied men participated in hemodynamic, temperature, catecholamine and respiratory measurements for 60 min during three consecutive stages: baseline (10 min; 33 °C water through a thin-tubed whole-body suit), mild cold stress (20 min; 25 °C water), and post-cold recovery (30 min; 33 °C water). Static CA was determined as the ratio between mean changes in middle cerebral artery blood velocity and MAP, dynamic CA as transfer function coherence, gain, and phase between spontaneous changes in MAP to middle cerebral artery blood velocity. MAP increased in both groups during cold and post-cold recovery (mean differences: 5–10 mm Hg; main effect of time: p= 0.001). Static CA was not different between the able-bodied vs. the cervical SCI group (mean (95% confidence interval (CI)) of between-group difference: −4 (−11 to 3) and −2 (−5 to 1) cm/s/mm Hg for cold (p= 0.22) and post-cold (p= 0.24), respectively). At baseline, transfer function phase was shorter in the cervical SCI group (mean (95% CI) of between-group difference: 0.6 (0.2 to 1.0) rad; p= 0.006), while between-group differences in changes in phase were not different in response to the cold stress (interaction term: p= 0.06). This pilot study suggests that static CA is similar between individuals with cervical SCI and able-bodied controls in response to moderate increases in MAP, while dynamic CA may be impaired in cervical SCI because of disturbed sympathetic control.

To compare the activity and walking pattern of individuals with chronic obstructive pulmonary disease (COPD) and control subjects during a 24‐hour period. Cross‐sectional study in home and community. The average walking velocity, time spent in sitting, standing, and lying, and numbers of steps per 24 hours were measured in nine individuals with COPD and eight healthy control subjects. The average walking velocity in individuals with COPD was equivalent to that of the control subjects. Individuals with COPD walked significantly less than the control subjects. The total time spent sitting, standing, and walking was similar in the two groups. The results suggested that the walking velocity selected by individuals with COPD serves to minimize energy cost per distance. The study findings emphasize the need to maintain walking velocity in any exercise prescription for individuals with COPD.

Mizushima T, Tajima F, Aoki S, Yamamoto M, Ogata H. Carotid artery flow volume and velocity by duplex sonography in men with chronic low thoracic and lumbar spinal cord injury.

Nakamura T, Mizushima T, Yamamoto M, Kawazu T, Umezu Y, Tajima F. Muscle sympathetic nerve activity during isometric exercise in patients with cerebrovascular accidents.

Objective: To investigate cardiovascular responses to orthostatic stress in patients with cerebrovascular accidents (CVA). Methods: Twelve male patients with CVA, 11 healthy elderly and 12 healthy young males participated in the present study. The CVA patients had suffered stroke with hemiplegia at least 11 months prior to the study, their medical conditions were stable, and no subjects were taking medications affecting the cardiovascular system. Heart rate (HR) was determined using RR intervals from the ECG. Stroke volume (SV) was estimated by an impedance method, and cardiac output (CO) was calculated by multiplying SV by HR. Blood pressure (BP) was determined by the auscultatory method. SV, HR, CO and BP were measured every 2 min before and during 7 min of 60-degree head-up tilt (HUT). Results: SV decreased and HR increased immediately after starting HUT in all groups. CO in healthy elderly and young subjects immediately decreased during HUT also, and the decrease was sustained throughout the head-up period. However, CO in CVA patients remained constant throughout the experiment. HUT immediately decreased SBP in all groups and the magnitude of initial SBP reduction in CVA patients was greater than that in the other groups. Conclusions: We identified an initial reduction of BP during HUT in CVA patients and the recovery of BP by 3 min of head-up tilt. We emphasize that adjustment to orthostatic stress in CVA patients should be practiced by HUT, as our findings showed that CVA patients maintained physiological orthostatic tolerance except for the initial fall in BP.

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The pathogenesis and underlying lesion of acquired idiopathic generalized anhidrosis (AIGA) are apparently heterogeneous. We report a patient with AIGA in whom the eccrine glands were histologically normal. However, electron microscopic examination showed markedly low numbers of nerve terminals and unmyelinated axons associated with the eccrine glands. Our laboratory investigations suggest that degeneration of postganglionic sympathietic cholinergic nerve may be the underlying pathogenetic mechanism of anhidrosis in this patient.

Blood pressure response to head-up tilt (HUT) in 7 healthy subjects and 9 patients before and after coronary artery bypass grafting (CABG) was measured during supine and 15-min 60° HUT. Stroke volume (SV) and ejection fraction (EF) were assessed by echocardiography. Baseline mean arterial pressure (MAP) and heart rate (HR) in patients before CABG were similar to healthy subjects. MAP in patients decreased by 6 (4–9) mmHg [median (1st–3rd quartiles)] during 7–12 mmHg of HUT with decreased cardiac output (CO = SV × HR) while HR remained unchanged. MAP in healthy subjects remained unchanged during HUT with increased HR. Body weight decreased by 3.5 (2.5–3.7) kg and MAP decreased by 6 (2–13) mmHg during the last 3-min HUT while HR increased after CABG. Decreases in SV and CO during HUT disappeared after CABG. Blood pressure decreased during HUT in patients before and after CABG regardless of HR response.