Assessing Motor Function in Congenital Muscular Dystrophy Patients Using Accelerometry.

BACKGROUND: When tested in a controlled clinic environment, individuals with neuromuscular-related symptoms may complete motor tasks within normal predicted ranges. However, measuring activity at home may better reflect typical motor performance. The accuracy of accelerometry measurements in individuals with congenital muscular dystrophy (CMD) is unknown. We aimed to compare accelerometry and manual step counts and assess free-living physical activity intensity in individuals with CMD using accelerometry. METHODS: Ambulatory pediatric CMD participants (n = 9) performed the 6-minute walk test in clinic while wearing ActiGraph GT3X accelerometer devices. During the test, manual step counting was conducted to assess concurrent validity of the ActiGraph step count in this population using Bland-Altman analysis. In addition, activity intensity of 6 pediatric CMD participants was monitored at home with accelerometer devices for an average of 7 days. Cut-point values previously validated for neuromuscular disorders were used for data analysis. RESULTS: Bland-Altman and intraclass correlation analyses showed no concurrent validity between manual and ActiGraph-recorded step counts. Fewer steps were recorded by ActiGraph step counts compared with manual step counts (411 ± 74 vs 699 ± 43, respectively; P = .004). Although improved, results were in the same direction with the application of low-frequency extension filters (587 ± 40 vs 699 ± 43, P = .03). ActiGraph step-count data did not correlate with manual step count (Spearman ρ = 0.32, P = .41; with low-frequency extension: Spearman ρ = 0.45, P = .22). Seven-day physical activity monitoring showed that participants spent more than 80% of their time in the sedentary activity level. CONCLUSIONS: In a controlled clinic setting, step count was significantly lower by ActiGraph GT3X than by manual step counting, possibly because of the abnormal gait in this population. Additional studies using triaxial assessment are needed to validate accelerometry measurement of activity intensity in individuals with CMD. Accelerometry outcomes may provide valuable measures and complement the 6-minute walk test in the assessment of treatment efficacy in CMD.

Upper extremity outcome measures for collagen VI-related myopathy and LAMA2-related muscular dystrophy.

Congenital muscular dystrophy (CMD) comprises a rare group of genetic muscle diseases that present at birth or early during infancy. Two common subtypes of CMD are collagen VI-related muscular dystrophy (COL6-RD) and laminin alpha 2-related dystrophy (LAMA2-RD). Traditional outcome measures in CMD include gross motor and mobility assessments, yet significant motor declines underscore the need for valid upper extremity motor assessments as a clinical endpoint. This study validated a battery of upper extremity measures in these two CMD subtypes for future clinical trials. For this cross-sectional study, 42 participants were assessed over the same 2-5 day period at the National Institutes of Health Clinical Center. All upper extremity measures were correlated with the Motor Function Measure 32 (MFM32). The battery of upper extremity assessments included the Jebsen Taylor Hand Function Test, Quality of Upper Extremity Skills Test (QUEST), hand held dynamometry, goniometry, and MyoSet Tools. Spearman Rho was used for correlations to the MFM32. Pearson was performed to correlate the Jebsen, QUEST, hand-held dynamometry, goniometry and the MyoSet Tools. Correlations were considered significant at the 0.01 level (2-tailed). Significant correlations were found between both the MFM32 and MFM Dimension 3 only (Distal Motor function) and the Jebsen, QUEST, MyoGrip and MyoPinch, elbow flexion/extension ROM and myometry. Additional correlations between the assessments are reported. The Jebsen, the Grasp and Dissociated Movements domains of the QUEST, the MyoGrip and the MyoPinch tools, as well as elbow ROM and myometry were determined to be valid and feasible in this population, provided variation in test items, and assessed a range of difficulty in CMD. To move forward, it will be of utmost importance to determine whether these upper extremity measures are reproducible and sensitive to change over time.

Comparison of sitting and supine forced vital capacity in collagen VI-related dystrophy and laminin α2-related dystrophy.

BACKGROUND: Progressive, restrictive, respiratory insufficiency is the major cause of morbidity and mortality in Congenital Muscular Dystrophy (CMD). Nocturnal hypoventilation precedes daytime alveolar hypoventilation, and if untreated, may lead to respiratory failure and cor pulmonale. CMD consensus care guidelines recommend screening for respiratory insufficiency by conventional and dynamic (sitting to supine) pulmonary function testing (PFT) and evaluating for sleep disordered breathing if there is more than 20% relative reduction from sitting to supine FVC(L) (ΔFVC). OBJECTIVE: The objective of this retrospective study was to explore and characterize dynamic FVC measures in 51 individuals with two common subtypes of CMD, COL6-RD, and LAMA2-RD. METHODS: We compared sitting and supine FVC in patients with confirmed mutation(s) in either COL6 or LAMA2. We investigated influences of age, CMD subtype, gender, race, ambulatory status, and non-invasive positive pressure ventilation (NIPPV) status on FVC percent predicted (FVCpp) and ΔFVC. RESULTS: COL6-RD participants exhibited a significant difference between sitting and supine mean FVCpp (sitting 66.1, supine 55.1; P < 0.0001) and were 5.4 times more likely to have -ΔFVC >20% than those with LAMA2-RD when controlling for ambulant status. FVCpp sitting correlated inversely with age in individuals ≤18 years. CONCLUSION: FVCpp sitting decreases progressively in childhood in both CMD subtypes. However, our results point to a difference in diaphragmatic involvement, with COL6-RD individuals having more disproportionate diaphragmatic weakness than LAMA2-RD. A ΔFVC of greater than -20% should continue to be used to prompt evaluation of sleep-disordered breathing. Timely initiation of NIPPV may be indicated to treat nocturnal hypoventilation. Pediatr Pulmonol. 2017;52:524-532. © 2017 Wiley Periodicals, Inc.

Results of a two-year pilot study of clinical outcome measures in collagen VI- and laminin alpha2-related congenital muscular dystrophies.

Potential therapies are currently under development for two congenital muscular dystrophy (CMD) subtypes: collagen VI-related muscular dystrophy (COL6-RD) and laminin alpha 2-related dystrophy (LAMA2-RD). However, appropriate clinical outcome measures to be used in clinical trials have not been validated in CMDs. We conducted a two-year pilot study to evaluate feasibility, reliability, and validity of various outcome measures, particularly the Motor Function Measure 32, in 33 subjects with COL6-RD and LAMA2-RD. In the first year, outcome measures tested included: Motor Function Measure 32 (MFM32), forced vital capacity (FVC) percent predicted sitting, myometry, goniometry, 10-meter walk, Egen Klassification 2, and PedsQL(TM) Generic and Neuromuscular Cores. In the second year, we added the North Star Ambulatory Assessment (NSAA), Hammersmith Functional Motor Scale (HFMS), timed functional tests, Measure of Activity Limitations (ACTIVLIM), Quality of Upper Extremity Skills Test (QUEST), and Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue subscale. The MFM32 showed strong inter-rater (0.92) and internal consistency (0.96) reliabilities. Concurrent validity for the MFM32 was supported by large correlations (range 0.623-0.936) with the following: FVC, NSAA, HFMS, timed functional tests, ACTIVLIM, and QUEST. Significant correlations of the MFM32 were also found with select myometry measurements, mainly of the proximal extremities and domains of the PedsQL(TM) scales focusing on physical health and neuromuscular disease. Goniometry measurements were less reliable. The Motor Function Measure is reliable and valid in the two specific subtypes of CMD evaluated, COL6-RD and LAMA2-RD. The NSAA is useful as a complementary outcome measure in ambulatory individuals. Preliminary concurrent validity of several other clinical outcome measures was also demonstrated for these subtypes.

Outcomes of cataract surgery in patients with uveitis: a systematic review and meta-analysis.

PURPOSE: To critically assess the evidence base regarding outcomes following cataract surgery in uveitic cases. DESIGN: Systematic evidence-based review and meta-analysis. METHODS: A comprehensive search query was performed on MEDLINE, EMBASE, CINHAL, and CENTRAL databases. Relevant publications were identified by reviewing query results and reference list searches. RESULTS: A total of 89 articles met eligibility criteria. Among uveitic eyes with quiet or mostly quiet uveitis before cataract surgery, 20/40 visual acuity or better (≥20/40) was achieved in 68% following phacoemulsification, 72% following extracapsular cataract extraction, and 40% following pars plana lensectomy. More eyes undergoing cataract surgery with intraocular lens (IOL) implantation than eyes left aphakic achieved ≥20/40 postoperatively (71% vs 52%). Eyes receiving acrylic IOLs or heparin-surface-modified (HSM) polymethylmethacrylate had better visual outcomes than those receiving non-HSM polymethylmethacrylate or silicone IOLs. Active uveitis at the time of cataract surgery was associated with worse visual outcomes. Compared with other uveitis cases, the proportion achieving 20/40 or better post cataract surgery was better for Fuchs heterochromic cyclitis cases and worse for uveitis related to Behçet disease, Vogt-Koyanagi-Harada disease, or sympathetic ophthalmia, and also posterior uveitis in general. CONCLUSION: Cataract surgery in eyes with uveitis resulted in normal range levels of visual acuity in most cases. The review suggests that preoperative control of uveitis, use of an acrylic or HSM IOL, and a diagnosis of Fuchs heterochromic cyclitis were associated with better outcomes. Posterior-involving uveitides tended to do worse, likely because of vision-limiting complications of uveitis. Average results may not be applicable to specific clinical scenarios.