Comparison of functional outcome scales in paediatric acute encephalitis: Responsiveness and outcome predictors

PURPOSE: To compare scoring systems and their ability to capture short and long-term recovery of paediatric patients with acute encephalitis. To identify clinical predictors of short-term outcomes by correlating functional outcome measures at 1 month post diagnosis of acute encephalitis. METHODS: Patients with encephalitis diagnosed between July 2011 and 2016 based on Granerod’s criteria were studied in this retrospective cohort study. Functional outcome scores on WeeFIM, LOS, GOS-E, mRS and ICF at initial presentation and 1, 3, 6 and 12 months later were compared. RESULTS: WeeFIM and LOS scores both showed maximum change in the first 3 months, reflecting highest recovery in this period. With WeeFIM, the greatest change occurred within the first month following diagnosis. On univariate analysis, seizure frequency in the first month, presence of movement disorder, presence of autonomic dysfunction and lower baseline functional score was associated with poorer WeeFIM scores at 1 month. The latter three variables remained statistically significant on multivariate analysis. CONCLUSION: WeeFIM is a potentially preferred functional outcome assessment tool as it demonstrated greatest recovery within the first month due to a trend of high responsiveness and relatively low ceiling effect. Presence of autonomic dysfunction and movement disorders at diagnosis correlated with poorer outcome at 1 month post diagnosis.

Natural history, outcome measures and trial readiness in LAMA2-related muscular dystrophy and SELENON-related myopathy in children and adults: protocol of the LAST STRONG study

Background SELENON (SEPN1)-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive proximal muscle weakness, early onset spine rigidity and respiratory insufficiency. A muscular dystrophy caused by mutations in the LAMA2 gene (LAMA2-related muscular dystrophy, LAMA2-MD) has a similar clinical phenotype, with either a severe, early-onset due to complete Laminin subunit α2 deficiency (merosin-deficient congenital muscular dystrophy type 1A (MDC1A)), or a mild, childhood- or adult-onset due to partial Laminin subunit α2 deficiency. For both muscle diseases, no curative treatment options exist, yet promising preclinical studies are ongoing. Currently, there is a paucity on natural history data and appropriate clinical and functional outcome measures are needed to reach trial readiness. Methods LAST STRONG is a natural history study in Dutch-speaking patients of all ages diagnosed with SELENON-RM or LAMA2-MD, starting August 2020. Patients have four visits at our hospital over a period of 1.5 year. At all visits, they undergo standardized neurological examination, hand-held dynamometry (age ≥ 5 years), functional measurements, questionnaires (patient report and/or parent proxy; age ≥ 2 years), muscle ultrasound including diaphragm, pulmonary function tests (spirometry, maximal inspiratory and expiratory pressure, sniff nasal inspiratory pressure; age ≥ 5 years), and accelerometry for 8 days (age ≥ 2 years); at visit one and three, they undergo cardiac evaluation (electrocardiogram, echocardiography; age ≥ 2 years), spine X-ray (age ≥ 2 years), dual-energy X-ray absorptiometry (DEXA-)scan (age ≥ 2 years) and full body magnetic resonance imaging (MRI) (age ≥ 10 years). All examinations are adapted to the patient’s age and functional abilities. Correlation between key parameters within and between subsequent visits will be assessed. Discussion Our study will describe the natural history of patients diagnosed with SELENON-RM or LAMA2-MD, enabling us to select relevant clinical and functional outcome measures for reaching clinical trial-readiness. Moreover, our detailed description (deep phenotyping) of the clinical features will optimize clinical management and will establish a well-characterized baseline cohort for prospective follow-up. Conclusion Our natural history study is an essential step for reaching trial readiness in SELENON-RM and LAMA2-MD. Trial registration This study has been approved by medical ethical reviewing committee Region Arnhem-Nijmegen (NL64269.091.17, 2017–3911) and is registered at ClinicalTrial.gov (NCT04478981).

First Regulatory Qualification of a Novel Digital Endpoint in Duchenne Muscular Dystrophy: A Multi-Stakeholder Perspective on the Impact for Patients and for Drug Development in Neuromuscular Diseases

<b><i>Background:</i></b> Functional outcome measures used to assess efficacy in clinical trials of investigational treatments for rare neuromuscular diseases like Duchenne muscular dystrophy (DMD) are performance-based tasks completed by the patient during hospital visits. These are prone to bias and may not reflect motor abilities in real-world settings. Digital tools, such as wearable devices and other remote sensors, provide the opportunity for continuous, objective, and sensitive measurements of functional ability during daily life. Maintaining ambulation is of key importance to individuals with DMD. Stride velocity 95th centile (SV95C) is the first wearable acquired digital endpoint to receive qualification from the European Medicines Agency (EMA) to quantify the ambulation ability of ambulant DMD patients aged ≥5 years in drug therapeutic studies; it is also currently under review for the US Food and Drug Administration (FDA) qualification. <b><i>Summary:</i></b> Focusing on SV95C as a key example, we describe perspectives of multiple stakeholders on the promise of novel digital endpoints in neuromuscular disease drug development.

Limited Scar Resection for Chronic Achilles Tendon Repair: Use of a Rat Model

Background: Achilles tendon rupture diagnosis is frequently missed, leading to the development of a chronic rupture that requires surgical intervention to remove scar tissue and return the elongated Achilles tendon to appropriate functional length. The limited scar resection (LSR) intervention strategy may provide an advantage over other techniques, as it is less invasive and nondestructive to other tissues, although there is little evidence comparing outcomes between intervention strategies. Hypothesis: The LSR technique would be a viable treatment option for chronic Achilles tendon ruptures and would perform comparably with a more clinically accepted procedure, the gastrocnemius fascial turndown (GFT), in postintervention functional outcome measures and tendon mechanical and histological properties. Study Design: Controlled laboratory study. Methods: Chronic Achilles tendon ruptures were induced in the right hindlimb of Sprague-Dawley rats by Achilles tendon transection without repair, immobilization in dorsiflexion, and 5 weeks of cage activity. Animals were randomly divided between the intervention strategy groups (LSR and GFT), received 1 week of immobilization in plantarflexion, and were sacrificed at 3 or 6 weeks postintervention. In vivo functional outcome measures (gait kinetics, passive joint function, tendon vascular perfusion) were quantified during healing, and tendon mechanical and histological properties were assessed postsacrifice. Results: When compared with the GFT, the LSR technique elicited a faster return to baseline in gait kinetics, although there were few differences between groups or with healing time in other functional outcome measures (passive joint function and vascular perfusion). Quasi-static mechanical properties were improved with healing in both surgical intervention groups, although only the LSR group showed an improvement in fatigue properties between 3 and 6 weeks postintervention. Histological properties were similar between intervention strategies, except for decreased cellularity in the LSR group at 6 weeks postintervention. Conclusion: The LSR technique is a viable surgical intervention strategy for a chronic Achilles tendon rupture in a rodent model, and it performs similarly, if not better, when directly compared with a more clinically accepted surgery, the GFT. Clinical Relevance: This study supports the increased clinical use of the LSR technique for treating chronic Achilles tendon rupture cases.

Outcomes of Corrective Surgery in Children with Foot Deformities Using Quantitative Gait Analysis

Objective. This study aimed to quantitatively define outcomes of corrective surgery in children with various foot deformities. Methods. We used a retrospective, nonrandomized design. All pediatric patients who underwent pre and post-operative gait analysis and corrective surgery were included. Outcome measures included quantitative gait analysis with temporospatial and kinematic parameters, the Gait Deviation Index, Gillette FAQ, and Hoffer’s criteria. Results. Five patients with neurogenic and idiopathic deformities underwent corrective surgery at the Philippine General Hospital from 2015 to 2017. Comparison of gait pre and postoperatively show promising outcomes, with improvement in GDI and FAQ levels, despite some of the patients’ need for braces. Conclusions. Quantitative gait analysis is a suitable method for evaluating surgical outcomes for foot deformity correction. It can be used in combination with functional outcome measures and clinical examination to give an overall picture of a patient’s walking ability.

Measuring recovery after open lower limb fractures: combined objective functional tests and global perceived recovery outperform narrower metrics and a standard generic patient reported outcome measure

Background Open lower limb fractures are serious injuries requiring combined ortho-plastic surgery and have significantly worse outcomes than similar closed fractures. There is little objective published data to determine which functional outcome measures best reflect progress or completeness of physical recovery. Our hypothesis was that objective measures combining strength, mobility and balance would better reflect recovery than isolated parameters (e.g. range of motion ROM) and would compare well to patients’ perceived recovery. Methods Adult open lower limb fracture patients were reviewed 6 and 12 weeks, 6, 9 and 12 months post-injury. The mechanism, injury pattern, age, gender and treatment were recorded. Isolated parameter objective functional outcome measures (OFOMs) (ROM and MRC strength grade) were compared to combined OFOMs (timed up and go, comfortable gait speed and fast gait speed, Edgren Side Step Test (TUAG, CGS, FGS, ESST) and Single Leg balance. Patient reported outcomes were recorded (Global Perceived Effect (GPE) score and Disability Rating Index (DRI)). Statistical analysis used non-parametric tests (e.g. Spearman correlation) compared each with time since injury. Results Sixty-eight patients (54 male) with a median age of 45(20–75) years. Of the 19 isolated OFOMs, only knee flexion and ankle plantar flexion ROM and strength improved with time (Spearman correlation p = 0.042, 0.008, 0.032, 0.036 respectively). TUAG, ESST, CGS, FGS and GPE scores showed significant improvement (Spearman correlation p < 0.001). Patients’ estimation of recovery paralleled these measures (Spearman correlation p < 0.001) with all but 2 patients achieving the minimum clinical important difference in DRI by 12 months compared to baseline. However, the GPE score had a higher proportion of improving responses than DRI at each time-point. Discussion Functional recovery is a key determinant in patients returning to work, providing for themselves and their family or resuming independent living for older patients. This study has demonstrated time-related improvements in combined OFOMs measuring mobility, strength, agility and balance paralleling patients’ perception of recovery in the 12 months after open lower limb fractures. Over the same time-frame, the simple GPE score compared favourably with the DRI. Such parameters could become part of a defined core outcomes set. Focussing rehabilitation towards these combined OFOMs may help hasten recovery. Trial registration South West Wales REC 06/WMW02/10).

Bilateral Patella Cartilage Debridement and Exercise Rehabilitation for Chondromalacia and Plica Syndrome: A Case Report

A 41-year-old active (exercising >600 min per week) male without a surgical history complained of nine years of intermittent bilateral anterior knee pain after physical activity. He was diagnosed with bilateral chondromalacia (grade IV chondrosis) with plica syndrome, for which he underwent bilateral patella cartilage debridement with medial plica excision (additional removal of lateral retinaculum in the right knee). The patient then performed 12 weeks of an aggressive postoperative rehabilitation program. Each rehabilitation session consisted of disinhibitory modalities (sensory level of transcutaneous electrical stimulation and cryotherapy: focal knee joint cooling and cold-water immersion) and voluntary exercises (aerobic, resistance, and flexibility). During rehabilitation, pain perception, knee joint skin temperature and circumference, and functional outcome measures (Kujala anterior knee pain scale, International Knee Documentation Committee Score, and lower-extremity functional scale) were also recorded. While the patient’s pathology and surgical intervention were not extreme, progressions in the rehabilitation components and functional outcome measures in this clinical case could be used as a future reference for postoperative interventions. Additionally, surgery-induced inflammation seemed to last for four weeks.