Muscle & Nerve最新文献

Introduction/aims: While dystrophinopathies are primarily characterized by progressive muscle weakness with onset during childhood, dystrophin also plays a role in brain development. This study aimed to characterize how neurodevelopmental and psychiatric disorders are currently identified and managed in clinical care of those with Becker and Duchenne muscular dystrophy (BDMD).

Methods: Parent Project Muscular Dystrophy (PPMD) disseminated surveys to caregivers and health care providers (HCPs) in the United States to assess the frequency and management of neurodevelopmental and psychiatric disorders of those with dystrophinopathy.

Results: 320 caregivers (C) and 74 HCPs responded to surveys. Caregivers indicated higher rates of neurodevelopmental and psychiatric disorders than HCPs, including anxiety (50.5% C, n = 112; 17.8% HCP, n = 19), attention-deficit hyperactivity disorder (ADHD) (32.0% C, n = 73; 15.9% HCP, n = 17), obsessive-compulsive disorder (OCD) (25.9% C, n = 57; 11.2% HCP, n = 12), depression (21.6% C, n = 48; 18.7% HCP, n = 20), and autism spectrum disorder (ASD) (21.0% C, n = 47; 10.3% HCP, n = 11). Results also indicated gaps in the assessment and care of these conditions, including lack of routine screening, reduced access to psychologists and psychiatrists, and lack of clarity amongst HCPs about who should manage neurodevelopmental and psychiatric concerns in those with dystrophinopathy.

Discussion: Closing the identified gaps in assessment, perception, and care will require increased awareness of neurodevelopmental and psychiatric conditions in dystrophinopathy and screening tools to facilitate early identification of these conditions during routine clinical care.

Introduction/aims: Immune-mediated necrotizing myopathy (IMNM) is an autoimmune myopathy. We aimed to compare clinical outcomes in patients with antibodies against 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) treated on immunotherapy regimens with and without maintenance intravenous immunoglobulin (IVIG). The secondary aim was to assess outcomes in a subset that received IVIG monotherapy.

Methods: This was a retrospective longitudinal cohort study. Multivariate logistic regression was used to analyze the association between IVIG and the probability of reaching normal creatine kinase (CK) and normal/near-normal proximal muscle strength at 3- and 6-month follow-ups. In patients treated with IVIG monotherapy, changes in CK and strength were analyzed using Wilcoxon signed rank tests.

Results: Patients treated with IVIG (n = 40) had higher odds of CK normalization at 6 months (OR 9.44, 95% CI 1.19-74.89, p = 0.03) although not at 3 months (p = 0.08) compared to patients not treated with IVIG (n = 13). Increased odds of normal/near-normal proximal muscle strength was not observed at 3 months (p = 0.14) or 6 months (p = 0.35). Subgroup analysis of patients on IVIG monotherapy (n = 15) showed a median CK reduction of 84.5% at 3 months (p < 0.001) and 95.7% at 6 months (p < 0.001). CK normalized in 40% by 6 months. Proximal muscle strength improved at 3 months (p = 0.003) and 6 months (p = 0.008). 76.9% had normal/near-normal proximal strength by 6 months.

Discussion: Patients treated with immunotherapy regimens that included IVIG were more likely to reach normal CK at 6 months. Maintenance IVIG monotherapy also induced marked improvements in CK and strength. IVIG monotherapy can be an effective first-line treatment for HMGCR IMNM.

Introduction/aims: The rising use of disease-modifying therapy is progressively impacting the health-related quality of life (HRQoL) of patients with spinal muscular atrophy (SMA) in their daily lives. This study aimed to evaluate the changes in HRQoL and independence in children with later-onset SMA receiving longitudinal treatment with nusinersen.

Methods: Forty-nine pediatric patients with later-onset SMA (symptom onset after 6 months of age) and their caregivers were enrolled. The HRQoL of patients evaluated by the proxy-reported Pediatric Quality of Life Inventory 3.0 Neuromuscular Module (PedsQL NMM) and the independence level determined by the SMA Independence Scale-Upper Limb Module (SMAIS-ULM) were assessed. Caregiver HRQoL was assessed using the Pediatric Quality of Life Inventory Family Impact Module (PedsQL FIM). Motor function was recorded using the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM), with subsequent analysis of the correlation between motor function, HRQoL, and independence scores.

Results: A significant difference was observed across all domains of the proxy-reported PedsQL NMM and in the independence assessment over the 18-month follow-up period (p < 0.001). A positive correlation was identified between RULM and total PedsQL NMM scores (Pearson-r = 0.539, p < 0.001), as well as SMAIS-ULM scores (Spearman-rho = 0.507, p < 0.001). Scores in all modules of the PedsQL FIM improved over time (p < 0.001).

Discussion: This study demonstrates the longitudinal effects of nusinersen treatment on multifaceted aspects of SMA patients, as captured by patient-reported outcome measures (PROMs). The inclusion of PROMs should be considered as part of the SMA multidisciplinary assessment.

Introduction/aims: Primary hypokalemic periodic paralysis (HypoPP) can present with periodic paralysis and/or permanent muscle weakness. Permanent weakness is accompanied by fat replacement of the muscle. It is unknown whether the permanent muscle weakness is solely due to fat replacement or if other factors affect the ability of the remaining muscle fibers to contract. We aimed to investigate muscle fat replacement and contractility in persons with HypoPP-causing variants in CACNA1S and to compare the results to healthy controls.

Methods: In this cross-sectional study, we used T1-weighted and 2-point Dixon magnetic resonance imaging (MRI) to assess fat replacement of the muscle and stationary dynamometry to assess muscle strength. Contractility was determined by maximal muscle contraction divided by the contractile cross-sectional muscle area.

Results: We included 45 persons with HypoPP-causing variants in CACNA1S and data from 37 healthy controls. We found that fat fraction was increased in ankle dorsiflexors and knee extensors and flexors, and further found that muscle strength was decreased in knee extensors and flexors in persons with HypoPP-causing variants in CACNA1S compared to healthy controls. Additionally, we found decreased contractility of thigh muscles in persons with HypoPP-causing variants in CACNA1S compared to healthy controls.

Discussion: The decreased contractility could relate to skeletal muscle voltage-gated calcium channel dysfunction, subclinical attacks of paralysis, and/or changed muscle architecture, but this needs further investigation.

Introduction/aims: We aimed to determine differences in diaphragm thickness by including/excluding pleural and peritoneal membranes, the variability in diaphragm thickness over the apposition zone, and the predictors of diaphragm thickness and excursion measurements.

Methods: At least 10 male and female subjects were recruited for each decade of life. Spirometry, respiratory muscle strength, and the diaphragm ultrasound (US) measurements were performed. Multivariate linear regression was applied to determine associations between diaphragm US parameters, subject characteristics, spirometry, and respiratory muscle strength.

Results: In 156 subjects (mean 47.8 ± 17.7; 20-80 years of age), a significant difference in diaphragm thickness was found when comparing measurements that included and excluded the pleural and peritoneal membranes (mean 2.3 vs. 1.7 mm; average difference of 35% (95% CI [15.3-60]); p < 0.001), as well as the minimum and maximum diaphragm thicknesses at different locations over the apposition zone (mean 1.4 vs. 2.1 mm; p < 0.001). Adjusting for sex, age, height, sniff nasal inspiratory pressure, and forced vital capacity, a positive association was found between body mass index (BMI) and diaphragm thickness (β =0.024, p < 0.001, partial R ² = 0.31, 95% CI [0.018, 0.030]); a negative association was found with the thickening ratio (β = -0.013, p = 0.050, partial R ² = 0.04, 95% CI [-0.024, -0.002]).

Discussion: Caliper placement and the location of measurement over the apposition zone greatly affect diaphragm thickness, which is also associated with BMI. Therefore, a standardized protocol for measuring diaphragmatic thickness and excursion is desirable, and BMI should be considered when interpreting the results.

Introduction/aims: MScanFit and StairFit are two motor unit number estimation (MUNE) methods derived from a compound muscle action potential (CMAP) scan. This study aims to compare MScanFit and StairFit MUNE values by applying both methods to the same muscles.

Methods: CMAP scans were recorded from the extensor digitorum brevis (EDB) and abductor digiti minimi (ADM) muscles. MUNE was performed using the MScanFit and the StairFit programs.

Results: Twenty healthy subjects (30.1 ± 6.6 years; 11 males, 9 females) participated in the study. The MScanFit and StairFit MUNE values were 79 ± 35 and 63 ± 20 for the EDB muscle, and 124 ± 33 and 80 ± 20 for the ADM muscle, respectively. The StairFit MUNE was significantly lower than the MScanFit MUNE (p < 0.05 for EDB, p < 0.01 for ADM).

Discussion: The different results for MScanFit and StairFit MUNE are likely due to the different strategies used by the two methods. Serial studies are needed to further compare their performances in tracking motor unit number and size changes.