Nonambulatory Patients Research Articles

Rib-on-Pelvis Deformity and Reported Pain in Neuromuscular Early-Onset Scoliosis.

Neuromuscular early-onset scoliosis (N-EOS) often presents with a long sweeping thoracolumbar scoliosis and pelvic obliquity. With severe pelvic obliquity, the ribs come into contact with the high side of the pelvis, termed rib-on-pelvis deformity (ROP). The goal of this study is to evaluate whether ROP is associated with reported pain and other health-related quality of life (HRQOL) measures. We hypothesize that ROP is associated with increased pain and negative HRQOL. A multicenter international registry was queried for all nonambulatory patients with N-EOS from 2012 to 2022. Both surgical and nonsurgical patients were included. ROP was classified as a binary radiographic assessment of preoperative (surgical patients) and most recent follow-up (nonsurgical patients) upright radiographs. Reported pain and other HRQOL measures were assessed through the 24-Item Early Onset Scoliosis Questionnaire (EOSQ-24). Patients with nonupright radiographs or EOSQ-24 questionnaires and corresponding radiographs >4 months apart were excluded. Totally, 225 patients (8.4±3.1y, 55% female) were included. The median major curve was 63.3 (IQR: 40.6 to 81.2) degrees and median pelvic obliquity was 15.5 degrees (IQR: 8.8 to 26.4). Eighty-three patients (37%) had ROP. ROP was associated with both frequency (P<0.001) and severity (P<0.001) of pain. ROP was associated with worse general health (P=0.01), increased difficulty with vocalization (P=0.02), increased frequency of shortness of breath (P=0.002), and increased difficulty sitting upright (P=0.04). Regarding overall EOSQ-24 domains, ROP was associated with worse general health, pain/discomfort, pulmonary function, and physical function (P<0.01). In a subanalysis of 76 patients who underwent surgical intervention with at least 2 years of follow-up, patients with preoperative ROP experienced significantly greater improvements in both frequency (P=0.004) and severity (P=0.001) of pain than the patients without preoperative ROP at 2 years postoperatively. The overall incidence of ROP in N-EOS is about 37%. ROP is associated with greater pain and worse HRQOL through the EOSQ-24 questionnaire. Furthermore, these patients experienced a greater reduction in pain after surgery. Clinicians and parents must be aware that ROP is possibly a pain generator, but responds positively to surgical intervention. Level III.

The Recovered Independent Ambulation Rate and Prognostic Factors of Non-ambulatory Patients After Metastatic Spinal Cord Compression Surgery.

Surgery could regain the ability to walk even in non-ambulatory patients with spinal cord compression due to metastatic spine disease. However, many patients cannot reach the stage of independent ambulation because most are at an advanced disease stage. This study investigated the regained independent ambulation rate after surgery and prognostic factors for independent ambulation after metastatic spinal cord compression surgery. In a retrospective cohort study, 38 non-ambulatory patients with spinal metastases at the cervical or thoracic lesions, who underwent surgery, were included. All surgeries were performed using laminectomy and posterior fixation. Recovery rates of independent ambulation and its prognostic factors were examined. Independent ambulation was defined as the use of a walking aid without wheelchair requirement. Factors, including age, tumor type, visceral organ metastasis, past systematic cancer therapy, neurological grade, the time from leg-symptom onset to non-ambulatory stage, and the time from non-ambulatory stage to surgery, were investigated. The regained independent ambulation rate was 18% (7/38). Compared to non-ambulatory patients, those who regained independent ambulation were more likely to have less past systematic therapy (14% [1/7] vs. 74% [23/31], P=0.003) and slow paralysis progression (over seven days from leg-symptom onset to non-ambulatory stage) (86% [6/7] vs. 23% [7/31], P=0.002). Recovery to independent ambulation in non-ambulatory patients with metastatic spinal cord compression was poor, even if surgery was performed. Absence of past systematic therapy and slow paralysis progression were favorable factors for regaining independent ambulation.

Discriminatory Properties of Quality-Adjusted Life-Years-Based Cost-Effectiveness Analyses for Patients With Disabilities: A Duchenne Muscular Dystrophy Case Study

ObjectivesQuality-adjusted life-years (QALYs) have been challenged as a measure of benefit for people with disabilities, particularly for those in low-utility health states or with irreversible disability. This study examined the impact of a QALY-based assessment on the price for a hypothetical treatment for Duchenne muscular dystrophy (DMD), a progressive, genetic neuromuscular disease. MethodsA previously published, 5-state model, which analyzed treatments for early ambulatory (EA) DMD patients, was replicated, validated, and adapted to include early nonambulatory (ENA) DMD patients. The model was used to assess a QALY-based threshold price (maximum cost-effective price) for a hypothetical treatment for 13-year-old ENA and 5-year-old EA patients (initial health states with lower and higher utility, respectively). All inputs were replicated including willingness-to-pay thresholds of $50 000 to $200 000/QALY. ResultsIn contrast to EA patients, ENA patients had a 98% modeled decline in QALY-based threshold price at a willingness-to-pay off $150 000/QALY or higher, despite equal treatment benefit (delayed progression/death). At $100 000/QALY or lower, net nontreatment costs exceeded health benefits, implying any treatment for ENA patients would not be considered cost-effective, even at $0 price, including an indefinite pause in disease progression. ConclusionsFor certain severe, disabling conditions, traditional approaches are likely to conclude that treatments are not cost-effective at any price once a patient progresses to a disabled health state with low utility value. These findings elucidate theoretical/ethical concerns regarding potential discriminatory properties of traditional QALY assessments for people with disabilities, particularly those who have lost ambulation or have other physical limitations.

Pelvic Fixation for Non-Ambulatory Patients with Neuromuscular Scoliosis Treated with Magnetically Controlled Growing Rods-A 4-Year Comparison of Two Different Fixation Methods.

Background/Objectives: This study aims to analyze the efficacy and safety of the two pelvic fixation systems, S-hooks (SH) and lumbar-sacral-alar-iliac (SAI) screws, when used in association with magnetically controlled growing rods (MCGRs) in non-ambulatory children with severe neuromuscular scoliosis (NMS). Methods: Forty-one patients were retrospectively examined and subdivided corresponding to ilium hook fixation or SAI screws. The major curve correction (%) and pelvic obliquity (PO) correction (%) were assessed utilizing scoliosis plain film radiographs over time. Complications and unplanned return to the operating room (UPROR) were recorded. Patient-specific pre- and postoperative values were included in a backward stepwise regression model to assess UPROR. Results: Mean age at index intervention was 9.4 years. Preoperative main curve was 81° and PO was 22°. 21 and 20 patients were categorized into the SH and SAI subgroups, respectively. Initial curve correction was significantly better in the SAI subgroup (63 vs. 42% in the SH, p = 0.045), while PO correction was equally good. Curve and PO correction were maintained throughout the follow-up period of 55 months. UPROR rate was 38% in the SH subgroup, and 5% in the SAI subgroup (p = 0.010). Regression analysis identified postoperative curve correction as predictive value for UPROR (p = 0.006). Conclusions: SAI screw fixation has a low UPROR rate and achieves superior curve correction. S-hooks are a viable option to correct PO and NMS in children with high operative risk to reduce operative time, but revision surgery is not uncommon.

Combined effects of strength and balance training versus aerobic training on balance, neuropathy symptoms and quality of life in patients with diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) occurs in >50% of diabetic patients and is a high risk-factor of balance problems and risk of falls. Impaired balance can lead to reduced function, which has a detrimental effect on patients' quality of life. Structured strength and balance training can result in sustained improvements in muscle strength, coordination, balance, functional status and quality of life. To determine the combined effects of strength and balance training versus aerobic training on balance, severity of symptoms of DPN, and quality of life in patients with DPN. This double blinded, two arm parallel design Randomized Clinical Trial. The study was conducted from March to December 2020 in the AIMS diabetic center Peshawar, Pakistan. Participants were selected through convenience sampling technique and randomly allocated into strength plus balance and aerobic training groups. Type 2 diabetic patients of both sexes, aged 40 to 80years, with a Toronto neuropathy score ≥6 recruited, while patients with ulceration/infection of feet, medical/Surgical conditions, and non-ambulatory patients were excluded from this study. Intervention was applied 3days a week for 8weeks. The Toronto clinical neuropathy system was used to assess neuropathy severity, SF-36 to assess quality of life and the Berg balance scale was used for assessment of balance. Assessment was done at the baseline and after 8weeks of intervention using SPSS. Version 22 was used for analysis. The mean age of the participants was 60.80±9.73. Between group analysis, which showed were statistically insignificant for neuropathy severity, balance and all domains of quality of life (p-value >0.05) except SF-36 General Health Perception Score, with Mean±SD of 62.50±7.54 in group A versus Mean±SD of in group B 60.00±15.98 (p-value=0.05). Within group analysis showed statistically significant results for neuropathy severity, balance and all domains of quality of life (p-value<0.05). This study concluded that there is a statistically significant effect of structured balance and strength training and aerobic training on severity of DPN, balance and quality of life. But there was no statistically significant difference in improvement between the two intervention groups.

Functional trajectories before and after loss of ambulation in Duchenne muscular dystrophy and implications for clinical trials.

This study examined functional trajectories of subjects during the transition phase between ambulatory and non-ambulatory Duchenne muscular dystrophy (DMD) to inform clinical trial designs for new therapeutics. Ambulatory, pulmonary, and upper limb function leading up to loss of ambulation (LoA) and non-ambulatory measures following LoA were quantified; time ordering of pulmonary and upper limb milestones relative to LoA were determined; and the 10-second time threshold for 10-meter walk/run (10MWR) as a marker of approaching LOA was explored. Included in this analysis were 51 subjects aged between 7 and 18 years who experienced LoA during follow-up in the PRO-DMD-01 natural history study. Mean age at LoA was 12.7 (7.1-18.6) years. Mean annual rates of decline in forced vital capacity (FVC) <80%-predicted and performance of upper limb (PUL) 1.2 total score were smaller before than after LoA, but not significantly (FVC %-predicted: 5.6% vs. 10.1%, p = 0.21; PUL 1.2 total score: 2.3 vs. 3.8 units, p = 0.20). More than half of patients experienced clinically significant deficits in FVC %-predicted and PUL 1.2 before experiencing LoA. Among subjects with baseline 10MWR >10 s, those with <1 year to LoA had similar mean ages but significantly worse mean ambulatory function at baseline compared to those with ≥1 year to LoA. Enriching DMD clinical trials for patients with declining pulmonary or upper limb function is achievable without restricting enrollment to non-ambulatory patients. The sequencing of LoA and initial deficits in pulmonary and upper limb function varied across patients and highlights the potential for composite outcomes or multi-outcome trial designs to assess disease-modifying therapies more comprehensively.

Nonselective lumbosacral ventral-dorsal rhizotomy for the management of lower-limb hypertonia in nonambulatory children with cerebral palsy.

Children with cerebral palsy (CP) often experience medically refractory hypertonia, for which there are surgical therapies including neuromodulation and rhizotomy. Traditional surgical treatment for medically refractory mixed hypertonia or dystonia includes intrathecal baclofen pumps and selective dorsal rhizotomy. A nonselective lumbosacral ventral-dorsal rhizotomy (VDR; ventral and dorsal roots lesioned by 80%-90%) has the potential to address the limitations of traditional surgical options. The authors highlighted the institutional safety and efficacy of nonselective lumbosacral VDR for palliative tone management in nonambulatory patients with more severe CP. The authors performed a retrospective analysis of patients who had undergone lumbosacral VDR between 2022 and 2023. Demographic factors, clinical variables, and operative characteristics were collected. The primary outcomes of interest included tone control and quality of life improvement. Secondary outcome measures included, as a measure of safety, perioperative events such as paresthesias. Postoperative complications were also noted. Fourteen patients (7 female) were included in the study. All patients had undergone a T12-L2 osteoplastic laminoplasty and bilateral L1-S1 VDR. Nine patients had quadriplegic mixed hypertonia, 4 had quadriplegic spasticity, and 1 had generalized secondary dystonia. Following VDR, there was a significant decrease in both lower-extremity modified Ashworth Scale (mAS) scores (mean difference [MD] -2.77 ± 1.0, p < 0.001) and upper-extremity mAS scores (MD -0.71 ± 0.76, p = 0.02), with an average follow-up of 3 months. In the patient with generalized dystonia, the lower-extremity Barry-Albright Dystonia Scale score decreased from 8 to 0, and the overall score decreased from 32 to 13. All parents noted increased ease in caregiving, particularly in terms of positioning, transfers, and changing. The mean daily enteral baclofen dose decreased from 47 mg preoperatively to 24.5 mg postoperatively (p < 0.001). Three patients developed wound dehiscence, 2 of whom had concurrent infections. Lumbosacral VDR is safe, is effective for tone control, and can provide quality of life improvements in patients with medically refractory lower-limb mixed hypertonia. Lumbosacral VDR can be considered for palliative tone control in nonambulatory patients with more severe CP. Larger studies with longer follow-ups are necessary to further determine safety and long-term benefits in these patients.

Palliative single-level selective dorsal rhizotomy for children with spastic cerebral palsy Gross Motor Function Classification System level IV and V: a case series and systematic review of the literature.

Single-level selective dorsal rhizotomy (SDR), typically indicated for ambulatory patients, is a controversial topic for severe spastic cerebral palsy (CP) with Gross Motor Function Classification System (GMFCS) level IV or V. The objective of this case series and systematic literature review was to outline the indication and outcome of palliative SDR for nonambulatory patients with CP and GMFCS level IV and V, focusing on improvement of spasticity and of patient and caregiver reported quality of life assessment. A retrospective case series of patients with CP and GMFCS level IV or V who underwent single-level SDR at the authors' institution is presented. Furthermore, two databases (PubMed and Embase) were searched and a systematic review with a search string based on the terms "selective dorsal rhizotomy," "cerebral palsy," and "outcome" was conducted. The primary outcome was the reduction of spasticity based on the modified Ashworth scale (MAS). Secondary outcomes were change on the Gross Motor Function Measure-66 (GMFM-66), evaluation of patient-reported outcome measures (PROMs), surgical morbidity, and mortality. Eleven consecutive children under the age of 25 years undergoing palliative single-level SDR were included. All patients showed a reduction in MAS score (mean 1.09 ± 0.66 points) and no surgical morbidity and mortality occurred. For the systematic review results from our case series, in addition to 4 reports, 274 total patients were included. Reduction of spasticity based on MAS score was noted in all studies (mean range 1.09-3.2 points). Furthermore, in 2 studies spasticity of the upper extremities showed a MAS score reduction as well (range 1.7-2.8 points). The GMFM-66 score improved in 72% of the patients, while bladder function improved in 78% of the patients. Based on the PROMs, 92% of the patients/caregivers were satisfied with the outcome and their quality of life after the procedure. Two wound infections (2.7%) and one CSF leak (1.3%) occurred, while no surgery-related deaths were described. This analysis showed an improvement in spasticity, daily care, and comfort for patients with CP and GMFCS levels IV and V. Larger cohorts analyzing the outcome of palliative single-level SDR, based on the MAS, GMFM-66, and PROMs, are still needed and should be the focus of future studies. Systematic review registration no.: CRD42024495762 (https://www.crd.york.ac.uk/prospero/).

Evaluation of Serum Vitamin D Levels and its Association with Increased Risk of Pressure Ulcer among Non-Ambulatory Patients

Background: Pressure ulcers are a significant health concern for non-ambulatory patients, often resulting from prolonged immobility. Vitamin D, recognized for its role in skin health and wound healing, may influence the development of these ulcers. This study examines the relationship between serum vitamin D levels and the prevalence of pressure ulcers in individuals unable to walk or move independently. Objective: To explore the association between serum Vitamin D levels and the risk of pressure ulcers, aiming to contribute to the literature and improve patient outcomes through evidence-based healthcare practices. Methods: A cross-sectional study was conducted at Sheikh Zayed Hospital and Bahria International Hospital, Lahore, from August 2023 to January 2024. Seventy non-ambulatory patients were recruited using a non-probability convenient sampling method. The Braden scale was employed to assess pressure ulcer severity, and serum vitamin D levels were measured through blood samples. Results: Participants had a mean age of 38.5 years (SD = 6.27) and a mean non-ambulatory duration of 13.72 days (SD = 5.22). Gender distribution was 55.7% female and 44.3% male. Historical pressure ulcer incidence was 10%. The leading reasons for hospitalization were stroke (28.6%), neuromuscular conditions (31.4%), and road traffic accidents (38.6%). A significant positive correlation was found between Braden scale scores and vitamin D levels (11.91 ± 3.40 and 11.40 ± 3.40 respectively, Pearson correlation coefficient = 0.71, p &lt; 0.01). Conclusion: There is a significant association between low serum vitamin D levels and an increased risk of developing pressure ulcers in non-ambulatory patients, supporting the need for vigilant monitoring and management of vitamin D levels.

Can postoperative Cobb and pelvic obliquity corrections be predicted using supine traction X-rays in non-ambulatory patients with cerebral palsy fused to L5? A case series study.

This study aimed to determine whether Cobb and pelvic obliquity corrections can be predicted using supine traction radiographs in patients with cerebral palsy (CP) who underwent posterior spinal fusion (PSF) from T2/3 to L5. From January 2010 to January 2020, 167 non-ambulatory patients with CP scoliosis underwent PSF using pedicle screws in two quaternary centers with a minimum of 2 years follow-up (FU). Radiological measurements and chart reviews were performed. A total of 106 patients aged 15.6 ± 0.4 years were included. All patients had significant correction of the Cobb angle (MC), pelvic obliquity (PO), thoracic kyphosis (TK), and lumbar lordosis (LL) without loss of correction at the last FU (LFU). Curve flexibility was significantly correlated with Cobb correction (δMC) immediately postoperatively (p < 0.0001, r = 0.8950), followed by the amount of correction in pelvic obliquity under traction (δPOT) (p = 0.0252, r = 0.2174). For correction in PO (δPO), the most significant variable was δPOT (p < 0.0001, r = 0.7553), followed by curve flexibility (p = 0.0059, r = 0.26) and the amount of correction in Cobb under traction (p = 0.0252, r = 0.2174). Cobb and PO corrections can be predicted using supine traction films for non-ambulatory CP patients treated with PSF from T2/3 to L5. The variables evaluated were interconnected, reinforcing preoperative planning for these patients. Comparative large-scale studies on patient-related clinical outcomes are required to determine whether this predicted correction is associated with improved surgical outcomes and reduced complication rates. IV.

Long-term reoperation rates following spinal fusion for neuromuscular scoliosis in nonambulatory patients with cerebral palsy

PurposeTo describe the incidence of reoperation and factors contributing to surgical revision within a minimum of 10 years after spinal fusion for scoliosis in patients with nonambulatory cerebral palsy (CP).MethodsWe conducted a retrospective review of consecutive nonambulatory patients with CP who underwent primary spinal fusion at a single specialty care center with a minimum of 10 years from their index surgery (surgery dates 2001–2011). Causes of reoperation were classified as implant failure/pseudoarthrosis, surgical site infection (SSI), proximal junctional kyphosis, prominent/symptomatic implants, and implant removal. Reoperation rates with 95% confidence intervals were calculated for each time interval, and an actuarial survival curve was generated.Results144 patients met inclusion criteria (mean age = 14.3 ± 2.6 years, 62.5% male); 85.4% had 5 years follow-up data; and 66.0% had 10 years follow-up data. Estimates from the actuarial analysis suggest that 14.9% (95% CI: 10.0–22.0) underwent reoperation by 5 years postsurgery, and 21.7% (95% CI: 15.4–30.1) underwent reoperation by 10 years postsurgery. The most common causes for reoperation were implant failure/pseudoarthrosis, SSI, and prominent/symptomatic implants.ConclusionsTo our knowledge, this study is the largest long-term follow-up of nonambulatory patients with CP and neuromuscular scoliosis who underwent spinal fusion. Approximately 22% of these patients required reoperation 10 years after their index surgery, primarily due to implant failure/pseudoarthrosis, SSI, and prominent/symptomatic implants. Complications and reoperations continued throughout the 10 years period after index surgery, reinforcing the need for long-term follow-up as these patients transition into adulthood.Level of evidenceIII.

Functional outcomes following surgery for spastic hip adductor muscles in ambulatory and non-ambulatory adults.

To evaluate functional outcomes of surgery of spastic hip adductor muscles (obturator neurotomy with or without adductor longus tenotomy) in ambulatory and non-ambulatory patients, using preoperatively defined personalized goals. Retrospective observational descriptive study. Twenty-three patients with adductor spasticity who underwent obturator neurotomy between May 2016 and May 2021 at the Clinique des Cèdres, Cornebarrieu, France, were included. Postoperative functional results were evaluated in accordance with the Goal Attainment Scaling method. Patients were considered "responders" if their score was ≥ 0. Secondary outcomes included spasticity, strength, hip range of motion and change in ambulatory capacity. When data were available, a comparison of pre- and postoperative 3-dimensional instrumented gait analysis was also performed. Among the 23 patients only 3 were non-walkers. Seventeen/22 patients achieved their main goal and 14/23 patients achieved all their goals. Results were broadly similar for both walking goals (inter-knee contact, inter-feet contact, fluidity, walking perimeter, toe drag) and non-walking goals (intimacy, transfer, pain, posture, dressing). Surgery of spastic hip adductor muscles results in functional improvement in ambulation, hygiene, dressing and posture and can be offered to patients with troublesome adductor overactivity. The use of a motor nerve block is recommended to define relevant goals before the surgery.

Nusinersen therapy changed the natural course of spinal muscular atrophy type 1: What about spine and hip?

Spinal muscular atrophy type 1 has a devastating natural course and presents a severe course marked by scoliosis and hip subluxation in nonambulatory patients. Nusinersen, Food and Drug Administration-approved spinal muscular atrophy therapy, extends survival and enhances motor function. However, its influence on spinal and hip deformities remains unclear. In a retrospective study, 29 spinal muscular atrophy type 1 patients born between 2017 and 2021, confirmed by genetic testing, treated with intrathecal nusinersen, and had registered to the national electronic health database were included. Demographics, age at the first nusinersen dose, total administrations, and Children's of Philadelphia Infant Test of Neuromuscular Disorders scores were collected. Radiological assessments included parasol rib deformity, scoliosis, pelvic obliquity, and hip subluxation. Mean age was 3.7 ± 1.1 (range, 2-6), and average number of intrathecal nusinersen administration was 8.9 ± 2.9 (range, 4-19). There was a significant correlation between Children's of Philadelphia Infant Test of Neuromuscular Disorders score and the number of nusinersen administration (r = 0.539, p = 0.05). The correlation between Children's of Philadelphia Infant Test of Neuromuscular Disorders score and patient age (r = 0.361) or the time of first nusinersen dose (r = 0.39) was not significant (p = 0.076 and p = 0.054, respectively). While 93.1% had scoliosis, 69% had pelvic obliquity, and 60.7% had hip subluxation, these conditions showed no significant association with patient age, total nusinersen administrations, age at the first dose, or Children's of Philadelphia Infant Test of Neuromuscular Disorders scores. Disease-modifying therapy provides significant improvements in overall survival and motor function in spinal muscular atrophy type 1. However, progressive spine deformity and hip subluxation still remain significant problems in the majority of cases which would potentially need to be addressed.

Effectiveness and safety of pamidronate treatment in nonambulatory children with low bone mineral density.

Nonambulatory pediatric patients may have low bone mineral density (BMD) and increased risk of pathologic fractures. Though bisphosphonate therapy is the mainstream medical intervention in these children, clinical data regarding this treatment are limited. Therefore, this study aimed to evaluate the effectiveness and safety of bisphosphonate therapy in such children. We conducted a retrospective study of 21 nonambulatory children (Gross Motor Function Classification System level V) with BMD z-score ≤ -2.0 who were treated with intravenous pamidronate for at least 1 year. These patients received pamidronate every 4 months at a dose of 1.0 to 3.0 mg/kg for each cycle and had regular follow-ups for at least 1 year. The main outcome measures were changes in BMD, risk rate of fracture, biochemical data, and adverse events. The average duration of pamidronate treatment was 2.0±0.9 years, and the mean cumulative dose of pamidronate according to body weight was 7.7±2.5 mg/kg/yr. After treatment, the mean lumbar spine bone mineral content, BMD, and height-for-age-z-score-adjusted BMD z-score (BMDhazZ) significantly improved. The relative risk of fracture after treatment was 0.21 (p=0.0032), suggesting that pamidronate treatment reduced fracture incidence significantly. The increase in the average dose per body weight in each cycle significantly increased the changes in BMDhazZ. Pamidronate treatment improved the bone health of nonambulatory children with low bone density without any significant adverse events. Independent of cumulative dosage and duration of treatment, the effectiveness of pamidronate increased significantly with an increase in the average dose per body weight in subsequent cycles.

The role of ataluren in the treatment of ambulatory and non-ambulatory children with nonsense mutation duchenne muscular dystrophy - a consensus derived using a modified Delphi methodology in Eastern Europe, Greece, Israel and Sweden.

This paper details the results of an evaluation of the level of consensus amongst clinicians on the use of ataluren in both ambulatory and non-ambulatory patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). The consensus was derived using a modified Delphi methodology that involved an exploration phase and then an evaluation phase. The exploration phase involved 90-minute virtual 1:1 interviews of 12 paediatric neurologists who cared for 30-120 DMD patients each and had patient contact every one or two weeks. The respondents managed one to ten nmDMD patients taking ataluren. The Discussion Guide for the interviews can be viewed as Appendix A. Following the exploration phase interviews, the interview transcripts were analysed by an independent party to identify common themes, views and opinions and developed 43 draft statements that the Steering Group (authors) reviewed, refined and endorsed a final list of 42 statements. Details of the recruitment of participants for the exploration and evaluation phases can be found under the Methods section. A consensus was agreed (> 66% of respondents agreeing) for 41 of the 42 statements using results from a consensus survey of healthcare professionals (n = 20) experienced in the treatment of nmDMD. The statements with a high consensus suggest that treatment with ataluren should be initiated as soon as possible to delay disease progression and allow patients to remain ambulatory for as long as possible. Ataluren is indicated for the treatment of Duchenne muscular dystrophy that results from a nonsense mutation in the dystrophin gene, in ambulatory patients aged 2 years and older (see Summary of Product Characteristics for each country).

Timely Surgical Intervention Leads to Better Sustained Coverage after Reconstructive Hip Surgery in Patients with Cerebral Palsy.

In up to 45-90% of non-ambulatory patients with cerebral palsy (CP), progressive hip migration can be observed. The goal of this study was to determine whether the implementation of a national hip surveillance guideline affected the outcome of hip reconstructions. We reviewed 48 primary hip reconstructions at a median follow-up of 4.4 years. Surgical outcome was evaluated based on complication rates and radiographic evaluation postoperatively and at follow-up. Radiographic measurements included the migration percentage (MP), head-shaft angle and acetabular index. The impact of preoperative MP, postoperative MP, tone management, Gross Motor Function Classification System (GMFCS) classification and age on MP at follow-up were examined using a mixed model analysis. A decrease in preoperative MP was noted, from a median of 75.0% (2014) to 39.0% (2020). Lower preoperative MP showed a significant correlation to lower MP postoperatively (p = 0.012). Postoperative MP was a significant independent predictor of a lower MP at follow-up (p = 0.002). This study shows an improvement in the timing of hip reconstruction in patients with CP after implementation of the hip surveillance guideline. A reduction in preoperative MP resulted in improved postoperative outcomes. A lower postoperative MP was the most important predictor for sustained containment of the hip.

Ambulatory Status at Discharge Predicts Six-Month Mortality in Patients with COVID-19: A Retrospective Cohort Study.

This retrospective cohort study aimed to evaluate the association between ambulatory status at discharge and six-month post-discharge mortality among adults with coronavirus disease (COVID-19). We analyzed data from 398 patients aged over 18 admitted to a tertiary hospital in South Korea between December 2019 and June 2022. Patients were classified into two groups based on their ambulatory status at discharge: ambulatory (able to walk independently, n = 286) and non-ambulatory (unable to walk independently, requiring wheelchair or bed-bound, n = 112). Our analysis revealed that six-month survival rates were significantly higher in the ambulatory group (94.2%) compared to the non-ambulatory group (84.4%). Multivariate analysis identified ambulatory status at discharge (p = 0.047) and pre-existing malignancy (p = 0.007) as significant prognostic factors for post-discharge survival. This study highlights that the ability to walk independently at discharge is a crucial predictor of six-month survival in COVID-19 patients. These findings emphasize the need for interventions to improve the physical performance of non-ambulatory patients, potentially enhancing their survival prospects. This underscores the importance of targeted rehabilitation and physical therapy for the comprehensive care of COVID-19 survivors.

Risdiplam improves subjective swallowing quality in non-ambulatory adult patients with 5q-spinal muscular atrophy despite advanced motor impairment

Background5q-associated spinal muscular atrophy (SMA) is characterized by the progressive loss of motor neurons with consecutive weakness and atrophy of the limb, respiratory, and bulbar muscles. While trunk and limb motor function improve or stabilize in adults with SMA under nusinersen and risdiplam treatment, the efficacy on bulbar function in this age group of patients remains uncertain. However, it is important to assess bulbar dysfunction, which frequently occurs in the disease course and is associated with increased morbidity and mortality.MethodsBulbar function was evaluated prospectively in 25 non-ambulatory adults with type 2 and 3 SMA before and 4 and 12 months after risdiplam treatment initiation using the Sydney Swallow Questionnaire (SSQ) and the bulbar subscore of the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (b-ALSFRS-R). Extremity function was assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM).ResultsSubjective swallowing quality, measured with the SSQ, improved after 12 months of therapy with risdiplam. For the b-ALSFRS-R, a non-significant trend towards improvement was observed. The RULM score improved after 12 months of risdiplam therapy, but not the HFMSE score. HFMSE and RULM scores did not correlate with the SSQ but the b-ALSFRS-R score at baseline.ConclusionsThe improvement in subjective swallowing quality under risdiplam treatment, despite an advanced disease stage with severe motor deficits, strengthens the importance of a standardized bulbar assessment in addition to established motor scores. This may reveal relevant treatment effects and help individualize treatment decisions in the future.

Decreased quality of life in Duchenne muscular disease patients related to functional neurological and cardiac impairment.

In this prospective study involving 37 Duchenne muscular dystrophy (DMD) patients aged 8-18 years and older, we examined the impact of neurological and cardiac factors on quality of life (QoL). Our findings revealed a negative correlation between upper limb movement and overall mobility, self-service, and usual activities. Ambulatory and non-ambulatory DMD patients showed significant differences in mobility-related parameters. Cardiac evaluations demonstrated associations between mitral annular plane systolic excursion (MAPSE) and mobility-related aspects. The PEDSQL 3.0 neuromuscular model questionnaire further highlighted age-related and movement-related correlations with QoL. The loss of ambulatory status and reduced upper limb movement were negatively associated with QoL, while upper limb movement positively correlated with septal MAPSE. However, no significant associations were found between MAPSE and anxiety/depression. These findings underscore the multifaceted impact of DMD on QoL and emphasize the importance of considering both neurological and cardiac factors in comprehensive patient care.

Effects of robot-assisted gait training on motor performance of lower limb in poststroke survivors: a systematic review with meta-analysis.

This study aimed to investigate the effects of robot-assisted gait training (RAGT) on improving walking ability, and to determine the optimal dosage of task-specific training based on RAGT for stroke patients. Two investigators independently searched electronic databases, including PubMed, Embase, Cochrane Library, and Physiotherapy Evidence Database (PEDro) from inception to 31 January 2020. The study design was a systematic review with meta-analysis of randomized controlled trials (RCTs), comparing the intervention of RAGT plus conventional therapy to conventional therapy alone. RCTs mainly focus on lower limb motor function as the primary outcomes, while the secondary outcomes involve gait speed, walking distance, cadence, balance, and activities of daily living (ADL). Pooled effect estimates were calculated by comparing the change from baseline to the end of the study in each group. Twenty-eight RCTs were included. The pooled analysis showed that RAGT had a significantly short-term effect on improving lower limb function [standardized mean difference (SMD) 0.32, 95% CI 0.10 to 0.55]. Additionally, there were significant improvements in gait speed (MD 0.10, 95% CI 0.06 to 0.14) and ADL (SMD 0.17, 95% CI 0.02 to 0.32). Subgroup analyses indicated that RAGT lasting for 30-60 minutes per day over 4 weeks yielded a moderate effect size (SMD 0.53, 95% CI 0.16 to 0.90). Additionally, RAGT significantly promoted lower limb function recovery in the early stage after a stroke (SMD 0.33, 95% CI 0.07 to 0.58) or in non-ambulatory patients (SMD 0.35, 95% CI 0.10 to 0.59). RAGT demonstrated significant positive effects on lower limb function post-stroke. Our results provide additional evidence to support that RAGT is a potentially appropriate intervention to promote lower limb recovery in individuals who have had a stroke.