New-onset of rheumatic diseases following COVID-19 vaccination: the report of three cases and a literature review.

Vaccines against coronavirus disease 2019 (COVID-19) have been distributed in most countries for the prevention of onset and aggravation of COVID-19. Recently, there have been increasing numbers of reports on new-onset autoimmune and autoinflammatory diseases following COVID-19 vaccination, however, only little information is available on the long-term safety of these vaccines. Here, we experienced three cases of new-onset rheumatic diseases following COVID-19 vaccination, one case each of rheumatoid arthritis (RA), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE). The symptom onset ranged from one day to a few days following vaccination. The patients of AAV and SLE were treated successfully with glucocorticoid therapy, and the patient of RA died due to COVID-19. In the literature review of new-onset rheumatic diseases following COVID-19 vaccination, which including seven cases of RA, 37 cases of AAV and 18 cases of SLE, the mean time from vaccination to onset was approximately 11 to 12 days. Most cases improved with glucocorticoid, immunosuppressive drugs and biologic agents. Although such adverse effects are rare, and vaccines are useful in prevent onset and severity of infections, continued accumulation of similar cases is important in terms of examining the long-term safety and understanding pathogenic mechanism of rheumatic diseases.

New-onset Immune-mediated Necrotizing Myopathy and Trigeminal Neuropathy after SARS-CoV-2 mRNA Vaccination in a Patient with Rheumatoid Arthritis and Sjögren's Syndrome.

We present the case of a 42-year-old woman with rheumatoid arthritis and Sjögren's syndrome treated with adalimumab who developed immune-mediated necrotizing myopathy (IMNM) and trigeminal neuropathy after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. Trigeminal neuralgia and elevated serum creatine kinase levels emerged 12 days post-vaccination, followed by myalgia in the femoral muscles. IMNM was histologically diagnosed. The pathogenesis may involve molecular mimicry between the SARS-CoV-2 spike glycoprotein and autologous tissues triggered by vaccination. This case emphasizes the association between SARS-CoV-2 vaccination, tumor necrosis factor inhibitor, IMNM, and trigeminal neuropathy, as well as the importance of monitoring immune-mediated adverse events following SARS-CoV-2 vaccination in patients with autoimmune disease.

Encapsulating Peritoneal Sclerosis in Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Systemic Sclerosis.

We encountered a 57-year-old Japanese woman with encapsulating peritoneal sclerosis (EPS) in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis. The patient was admitted to our hospital because of ascites retention. Administration of tocilizumab, an anti-interleukin-6 receptor antibody, for her RA reduced the refractory ascites remarkably; however, she developed sudden acute gastrointestinal bleeding and died a year later. On autopsy, sclerotic thickening of the peritoneum showed diffuse infiltration of podoplanin-positive fibroblast-like cells, and a diagnosis of EPS was made. EPS rarely occurs in SLE, and tocilizumab may be a new treatment candidate for EPS.

New-onset Adult-onset Still's Disease Following COVID-19 Vaccination: Three Case Reports and a Literature Review.

Since December 2020, coronavirus disease 2019 (COVID-19) vaccines have been distributed in most countries to prevent the onset and aggravation of COVID-19. There is little information regarding the long-term safety of the vaccines. We report three cases and a literature review of new-onset adult-onset Still's disease (AOSD) that occurred following COVID-19 vaccination. Our cases include moderate to severe AOSD, and two were complicated with macrophage activation syndrome. Seventeen cases of new-onset or relapse of AOSD following COVID-19 vaccination, including 14 identified in the literature review and our 3 patients, were all treated successfully with glucocorticoid therapy, immunosuppressive drugs, or biologic agents.

Plasma pentraxin 3 is associated with progression of radiographic joint damage, but not carotid atherosclerosis, in female rheumatoid arthritis patients: 3-year prospective study.

Background: Pentraxin 3 (PTX3) has an important role in inflammation, immunity, and atherosclerosis. Rheumatoid arthritis (RA) is a chronic inflammatory disease featuring both joint damage and atherosclerosis. We investigated whether the plasma PTX3 level was associated with progression of joint destruction and subclinical atherosclerosis in RA patients.Methods: Plasma PTX3 levels were measured in 72 women with RA and 80 female control subjects. In RA patients, we also evaluated clinical characteristics, medications, and at one and three years, joint damage and atherosclerosis. Then we investigated whether PTX3 was associated with progression of joint destruction or an increase of carotid intima-media thickness (IMT).Results: Plasma PTX3 levels were significantly higher in the RA patients than in healthy controls (4.05 ± 2.91 ng/mL vs. 1.61 ± 1.05 ng/mL, p < .001). By multivariate linear regression analysis, the plasma pentraxin 3 level was independently associated with radiographic progression of joint damage for 3 years in the RA patients after adjustment for age, disease duration, body mass index, rheumatoid factor, MMP-3, Disease Activity Score 28-ESR, postmenopausal status, current use of corticosteroids and biologic use. On the other hands, pentraxin 3 was not associated with an increase of carotid intima-media thickness in RA patients.Conclusion: Female RA patients had elevated plasma PTX3 levels compared with control female subjects. PTX3 was independently associated with radiographic progression of joint damage in the RA patients, but not with carotid atherosclerosis.

Safety and immediate effects of Hybrid Assistive Limb in children with cerebral palsy: A pilot study.

PURPOSE: Early intervention is effective for developing motor ability and preventing contractures and deformities in patients with cerebral palsy (CP). Gait training using the newly developed Hybrid Assistive Limb (HAL) shows promise as an intervention to prevent deterioration in walking ability and deformities in pediatric CP patients. The purpose of this pilot study was to examine the safety and immediate effects on walking ability after gait training using the HAL in pediatric CP patients. METHODS: Nineteen patients (six females, 13 males; mean age 8.5 years; mean height 120.5 cm; mean weight 23.2 kg) were enrolled. The Gross Motor Functional Classification Scale level was I in two patients, II in two, III in eight, and IV in seven. The HAL was used for a single session of gait training. The primary outcome was safety of the HAL for use in pediatric CP patients. The secondary outcome was the immediate effect after gait training with HAL, evaluated by passive range of motion (ROM) and gait parameters, including gait speed (m/s), step length (cm), and cadence (step/min). RESULTS: All 19 patients were able to carry out the gait training without any severe adverse events. Significant improvements were observed for mean internal/external rotation and abduction angles of the hip joint, and ankle dorsiflexion angles (n = 19). Significant improvements were observed for mean gait speed and step length based on expansion of the hip flexion-extension range (n = 11). CONCLUSION: Gait training using the HAL is safe and can produce immediate improvements in ROM and walking ability in pediatric patients with CP.

Newly developed hybrid assistive limb for pediatric patients with cerebral palsy: a case report.

[Purpose] The effect of fitness training on improving walking ability in cerebral palsy is controversial. However, gait training with a wearable robot (hybrid assistive limb) has been reported to improve gait ability in patients with cerebral palsy. For pediatric patients, a smaller, lighter-weight hybrid assistive limb has been newly developed. We describe the immediate effect of this newly developed smaller hybrid assistive limb on the gait ability of a pediatric patient with cerebral palsy and examine its safety and feasibility. [Participant and Methods] An 11-year-old male with spastic cerebral palsy (height, 130 cm; weight, 29.0 kg) who could ambulate using an elbow crutch participated in this study. A single session of hybrid assistive limb training comprising pre-exercise of the hip and knee joints and walking for 20 minutes was conducted. [Results] The intervention immediately improved his gait speed, stride length, and cadence according to the 10-m walking test. Co-contraction of agonist/antagonist muscles during walking improved, and the flexion angle of the right hip during the swing phase increased, which resulted in symmetry of movement of both legs. [Conclusion] Gait training using the new, smaller hybrid assistive limb for a pediatric patient was safe and feasible, and the newly developed hybrid assistive limb has the potential to immediately improve walking ability even among young children with cerebral palsy.

Safety and immediate effect of gait training using a Hybrid Assistive Limb in patients with cerebral palsy.

[Purpose] This study aimed to determine the safety and immediate effect of a single training session with the Hybrid Assistive Limb (CYBERDYNE) on walking ability in patients with cerebral palsy. [Participants and Methods] This study included 20 patients with cerebral palsy (15 males, 5 females, mean age 15.0 ± 6.3 years; 19 with spastic cerebral palsy, 1 with athetoid cerebral palsy; Gross Motor Function Classification System level I: 4, II: 3, III: 9, and IV: 4). Participants completed a single 20-minute gait training session using the Hybrid Assistive Limb. The safety and immediate effect were evaluated. The immediate outcomes were gait speed and mean step length, and cadence before and after training. [Results] Two participants were excluded because they were not tall enough to use the Hybrid Assistive Limb. Eighteen participants performed the training. There were no serious adverse events during the training. Since 14 participants were able to walk on their own, walking evaluations were performed before and after training. Statistically significant improvements were observed in gait speed and mean step length. [Conclusion] Gait training using the Hybrid Assistive Limb is safe for patients with cerebral palsy and can produce immediate effects on walking ability in ambulatory patients with cerebral palsy.

Robot-assisted training using Hybrid Assistive Limb® for cerebral palsy.

PURPOSE: The Hybrid Assistive Limb® (HAL®, CYBERDYNE) is a wearable robot that provides assistance to a patient while they are walking, standing, and performing leg movements based on the wearer's intended movement. The effect of robot-assisted training using HAL® for cerebral palsy (CP) is unknown. Therefore, we assessed the effect of robot-assisted training using HAL® on patients with CP, and compared walking and gross motor abilities between pre-intervention and post-intervention. METHODS: Six subjects with CP were included (mean age: 16.8 years; range: 13-24 years; Gross Motor Function Classification System levels II-IV: n = 1, 4, 1). Robot-assisted training using HAL® were performed 2-4 sessions per week, 20 min per session, within a 4 weeks period, 12 times in total. Outcome measures included gait speed, step length, cadence, single-leg support per gait cycle, hip and knee joint angle in stance, and swing phase per gait cycle, 6-minute walking distance (6 MD), physiological cost index (PCI), knee-extension strength, and Gross Motor Function Measure (GMFM). RESULTS: There were significant increases in self-selected walking speed (SWS), cadence during SWS and maximum walking speed (MWS), single-leg support per gait cycle, hip joint angle in the swing phase, 6 MD, and GMFM. In contrast, gait speed during MWS, step length during SWS and MWS, hip and knee joint angle in the stance phase, knee joint angle in the swing phase, PCI, and knee-extension strength generally improved, but not significantly. CONCLUSION: Robot-assisted training using HAL® may improve walking and gross motor abilities of patients with CP.

Immediate effects of a single session of robot-assisted gait training using Hybrid Assistive Limb (HAL) for cerebral palsy.

[Purpose] Robot-assisted gait training (RAGT) using Hybrid Assistive Limb (HAL, CYBERDYNE) was previously reported beneficial for stroke and spinal cord injury patients. Here, we investigate the immediate effect of a single session of RAGT using HAL on gait function for cerebral palsy (CP) patients. [Subjects and Methods] Twelve patients (average age: 16.2 ± 7.3 years) with CP received a single session of RAGT using HAL. Gait speed, step length, cadence, single-leg support per gait cycle, hip and knee joint angle in stance, and swing phase per gait cycle were assessed before, during, and immediately after HAL intervention. [Results] Compared to baseline values, single-leg support per gait cycle (64.5 ± 15.8% to 69.3 ± 12.1%), hip extension angle in mid-stance (149.2 ± 19.0° to 155.5 ± 20.1°), and knee extension angle in mid-stance (137.6 ± 20.2° to 143.1 ± 19.5°) were significantly increased immediately after intervention. Further, the knee flexion angle in mid-swing was significantly decreased immediately after treatment (112.0 ± 15.5° to 105.2 ± 17.1°). Hip flexion angle in mid-swing also decreased following intervention (137.2 ± 14.6° to 129.7 ± 16.6°), but not significantly. Conversely, gait speed, step length, and cadence were unchanged after intervention. [Conclusion] A single-time RAGT with HAL improved single-leg support per gait cycle and hip and knee joint angle during gait, therapeutically improving gait function in CP patients.

Effect of botulinum toxin type A treatment in children with cerebral palsy: Sequential physical changes for 3 months after the injection.

PURPOSE: This study investigated the sequential physical changes after botulinum toxin type A (BTX-A) injected in children with cerebral palsy. METHODS: Nine children with cerebral palsy were included. Measurements were performed before treatment and 4 weeks, 8 weeks, and 12 weeks after treatment. We used video-recorded gait in the sagittal plane. The maximum flexion and extension angles of the hip, knee and ankle joints, step length, gait speed, and observational gait were measured using the Foot Contact Scale (FCS) and the Physician's Rating Scale (PRS). We also measured the lower limb range of motion (ROM), Modified Tardieu Scale (MTS), knee joint extension torque, and Gross Motor Function Measure-66 (GMFM-66). RESULTS: The ankle dorsiflexion ROM, GMFM-66, and the maximum dorsiflexion angle of the ankle during gait were significantly increased at 8 weeks after treatment, and knee joint extension torque was significantly increased at 12 weeks after treatment. CONCLUSION: Maximum effects of BTX-A treatment do not occur during the early stage after treatment. Therefore, long-term intervention with rehabilitation between BTX-A treatment may be more effective than implementing rehabilitation for only a brief period.

Use of Hybrid Assistive Limb (HAL®) for a postoperative patient with cerebral palsy: a case report.

BACKGROUND: The Hybrid Assistive Limb (HAL®) is an exoskeleton wearable robot suit that assists in voluntary control of knee and hip joint motion. There have been several studies on HAL intervention effects in stroke, spinal cord injury, and cerebral palsy. However, no study has investigated HAL intervention for patients with cerebral palsy after surgery. CASE PRESENTATION: We report a case of using HAL in a postoperative patient with cerebral palsy. A 15-year-old boy was diagnosed with spastic diplegia cerebral palsy Gross Motor Function Classification System level IV, with knee flection contracture, equinus foot, and paralysis of the right upper extremity with adduction contracture. He underwent tendon lengthening of the bilateral hamstrings and Achilles tendons. Although the flexion contractures of the bilateral knees and equinus foot improved, muscle strength decreased after the soft tissue surgery. HAL intervention was performed twice during postoperative months 10 and 11. Walking speed, stride, and cadence were increased after HAL intervention. Post HAL intervention, extension angles of the knee in stance phase and hip in the pre-swing phase were improved. In the gait cycle, the proportion of terminal stance in the stance and swing phase was increased. CONCLUSIONS: Hybrid Assistive Limb intervention for postoperative patients with cerebral palsy whose muscle strength decreases can enhance improvement in walking ability. Further studies are needed to examine the safety and potential application of HAL in this setting.