Claudia Senesac

T₂ mapping provides multiple approaches for the characterization of muscle involvement in neuromuscular diseases: a cross-sectional study of lower leg muscles in 5-15-year-old boys with Duchenne muscular dystrophy.

Skeletal muscles of children with Duchenne muscular dystrophy (DMD) show enhanced susceptibility to damage and progressive lipid infiltration, which contribute to an increase in the MR proton transverse relaxation time (T2). Therefore, the examination of T2 changes in individual muscles may be useful for the monitoring of disease progression in DMD. In this study, we used the mean T2, percentage of elevated pixels and T2 heterogeneity to assess changes in the composition of dystrophic muscles. In addition, we used fat saturation to distinguish T2 changes caused by edema and inflammation from fat infiltration in muscles. Thirty subjects with DMD and 15 age‐matched controls underwent T2‐weighted imaging of their lower leg using a 3‐T MR system. T2 maps were developed and four lower leg muscles were manually traced (soleus, medial gastrocnemius, peroneal and tibialis anterior). The mean T2 of the traced regions of interest, width of the T2 histograms and percentage of elevated pixels were calculated. We found that, even in young children with DMD, lower leg muscles showed elevated mean T2, were more heterogeneous and had a greater percentage of elevated pixels than in controls. T2 measures decreased with fat saturation, but were still higher (P < 0.05) in dystrophic muscles than in controls. Further, T2 measures showed positive correlations with timed functional tests (r = 0.23–0.79). The elevated T2 measures with and without fat saturation at all ages of DMD examined (5–15 years) compared with unaffected controls indicate that the dystrophic muscles have increased regions of damage, edema and fat infiltration. This study shows that T2 mapping provides multiple approaches that can be used effectively to characterize muscle tissue in children with DMD, even in the early stages of the disease. Therefore, T2 mapping may prove to be clinically useful in the monitoring of muscle changes caused by the disease process or by therapeutic interventions in DMD. Copyright

Locomotor Training Restores Walking in a Nonambulatory Child With Chronic, Severe, Incomplete Cervical Spinal Cord Injury

Background and Purpose: Locomotor training (LT) enhances walking in adult experimental animals and humans with mild-to-moderate spinal cord injuries (SCIs). The animal literature suggests that the effects of LT may be greater on an immature nervous system than on a mature nervous system. The purpose of this study was to evaluate the effects of LT in a child with chronic, incomplete SCI. Subject: The subject was a nonambulatory 4½-year-old boy with an American Spinal Injury Association Impairment Scale (AIS) C Lower Extremity Motor Score (LEMS) of 4/50 who was deemed permanently wheelchair-dependent and was enrolled in an LT program 16 months after a severe cervical SCI. Methods: A pretest-posttest design was used in the study. Over 16 weeks, the child received 76 LT sessions using both treadmill and over-ground settings in which graded sensory cues were provided. The outcome measures were ASIA Impairment Scale score, gait speed, walking independence, and number of steps. Result: One month into LT, voluntary stepping began, and the child progressed from having no ability to use his legs to community ambulation with a rolling walker. By the end of LT, his walking independence score had increased from 0 to 13/20, despite no change in LEMS. The childs final self-selected gait speed was 0.29 m/s, with an average of 2,488 community-based steps per day and a maximum speed of 0.48 m/s. He then attended kindergarten using a walker full-time. Discussion and Conclusion: A simple, context-dependent stepping pattern sufficient for community ambulation was recovered in the absence of substantial voluntary isolated lower-extremity movement in a child with chronic, severe SCI. These novel data suggest that some children with severe, incomplete SCI may recover community ambulation after undergoing LT and that the LEMS cannot identify this subpopulation.

Effects of trunk restraint combined with intensive task practice on poststroke upper extremity reach and function: a pilot study.

Background. Poststroke reaching is characterized by excessive trunk motion and abnormal shoulder—elbow coordination. Little attention is typically given to arm—trunk kinematics during task practice. Preventing compensatory trunk motion during short-term practice immediately improves kinematics, but effects of longer-term practice are unknown. Objective. This study compared the effects of intensive task practice with and without trunk restraint on poststroke reaching kinematics and function. Methods. A total of 11 individuals with chronic stroke, baseline Fugl-Meyer Upper Extremity Assessment scores 26 to 54, were randomized to 2 constraint-therapy intervention groups. All participants wore a mitt on the unaffected hand for 90% of waking hours over 14 days and participated in 10 days/6 hours/day of supervised progressive task practice. During supervised sessions, one group trained with a trunk restraint (preventing anterior trunk motion) and one group did not. Tasks for the trunk-restraint group were located to afford repeated use of a shoulder flexion—elbow extension reaching pattern. Outcome measures included kinematics of unrestrained targeted reaching and tests of functional arm ability. Results. Posttraining, the trunk-restraint group demonstrated straighter reach trajectories (P = .000) and less trunk displacement (P = .001). The trunk-restraint group gained shoulder flexion (P = .006) and elbow extension (P = .022) voluntary ranges of motion, the nonrestraint group did not. Posttraining angle—angle plots illustrated that individuals from the trunk-restraint group transitioned from elbow flexion to elbow extension during mid-reach; individuals in the nonrestraint group retained pretraining movement strategies. Both groups gained functional arm ability (P < .05 all tests). Conclusion. Intensive task practice structured to prevent compensatory trunk movements and promote shoulder flexion—elbow extension coordination may reinforce development of “normal” reaching kinematics.

Longitudinal measurements of MRI-T2 in boys with Duchenne muscular dystrophy: effects of age and disease progression.

Duchenne muscular dystrophy (DMD) is characterized by an increased muscle damage and progressive replacement of muscle by noncontractile tissue. Both of these pathological changes can lengthen the MRI transverse proton relaxation time (T2). The current study measured longitudinal changes in T2 and its distribution in the lower leg of 16 boys with DMD (5-13years, 15 ambulatory) and 15 healthy controls (5-13years). These muscles were chosen to allow extended longitudinal monitoring, due to their slow progression compared with proximal muscles in DMD. In the soleus muscle of boys with DMD, T2 and the percentage of pixels with an elevated T2 (⩾2SD above control mean T2) increased significantly over 1year and 2years, while the width of the T2 histogram increased over 2years. Changes in soleus T2 variables were significantly greater in 9-13years old compared with 5-8years old boys with DMD. Significant correlations between the change in all soleus T2 variables over 2years and the change in functional measures over 2years were found. MRI measurement of muscle T2 in boys with DMD is sensitive to disease progression and shows promise as a clinical outcome measure.

Participation and quality of life in children with Duchenne muscular dystrophy using the International Classification of Functioning, Disability, and Health.

BackgroundDuchenne muscular dystrophy (DMD) is characterized by muscle damage and progressive loss of muscle function in male children. DMD is one of the most devastating genetically linked neuromuscular diseases for which there is currently no cure. Most clinical studies for DMD utilize a standard protocol for measurement exploring pathophysiology, muscle strength and timed tasks. However, we propose that examining broader components of health as emphasized by the International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY) may be of great value to children and their families, and important outcomes for future clinical trials.MethodsFifty boys with DMD and 25 unaffected age-matched boys completed two self-report measures: the Children’s Assessment of Participation and Enjoyment and the Pediatric Quality of Life InventoryTM 4.0. We investigated differences between the two groups with regard to participation in life activities and perceived quality of life (QoL). Additionally, we compared participation in activities and QoL in both cohorts of younger and older boys.ResultsParticipation in physical activities was significantly lower in boys with DMD than unaffected boys. Perceived QoL was markedly diminished in children with DMD relative to unaffected controls, except in the emotional domain. The amount of time boys engage in an activity, as well as participation in social activities, declined for our older boys with DMD but no changes were observed for our older unaffected boys. For both groups, QoL remained constant over time.ConclusionsThe ICF-CY provides a conceptual framework and specific terminology that facilitates investigation of the consequences of impairment in children and youth. Our study is one of the first to explore participation in a cohort of boys with DMD. It was not surprising that activities of choice for boys with DMD were less physical in nature than unaffected boys their age, but the consequences of less social engagement as the boys with DMD age is of great concern. Results from our study underscore the need to further evaluate activities that children elect to participate in, with special emphasis on facilitators and barriers to participation and how participation changes throughout the course of a disease.

Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS

Objective: To evaluate the effects of corticosteroids on the lower extremity muscles in boys with Duchenne muscular dystrophy (DMD) using MRI and magnetic resonance spectroscopy (MRS). Methods: Transverse relaxation time (T2) and fat fraction were measured by MRI/MRS in lower extremity muscles of 15 boys with DMD (age 5.0–6.9 years) taking corticosteroids and 15 corticosteroid-naive boys. Subsequently, fat fraction was measured in a subset of these boys at 1 year. Finally, MRI/MRS data were collected from 16 corticosteroid-naive boys with DMD (age 5–8.9 years) at baseline, 3 months, and 6 months. Five boys were treated with corticosteroids after baseline and the remaining 11 served as corticosteroid-naive controls. Results: Cross-sectional comparisons demonstrated lower muscle T2 and less intramuscular (IM) fat deposition in boys with DMD on corticosteroids, suggesting reduced inflammation/damage and fat infiltration with treatment. Boys on corticosteroids demonstrated less increase in IM fat infiltration at 1 year. Finally, T2 by MRI/MRS detected effects of corticosteroids on leg muscles as early as 3 months after drug initiation. Conclusions: These results demonstrate the ability of MRI/MRS to detect therapeutic effects of corticosteroids in reducing inflammatory processes in skeletal muscles of boys with DMD. Our work highlights the potential of MRI/MRS as a biomarker in evaluating therapeutic interventions in DMD.

Bilateral Arm Training With Rhythmic Auditory Cueing in Chronic Stroke: Not Always Efficacious

Objective. Bilateral arm training with rhythmic auditory cueing (BATRAC) has been reported to be efficacious in promoting upper-extremity (UE) recovery in chronic stroke. We tested a modified form of BATRAC (modBATRAC) in a new group of participants with a condensed treatment regime to determine whether we could replicate these reported results. Methods. Fourteen subjects with chronic stroke completed 2 weeks of 2.25 hours per session, 4 sessions per week of modBATRAC. Results. No significant changes were observed in UE Fugl-Meyer or Wolf Motor Function Test scores. Subjects did report increased paretic UE use on the Motor Activity Log (mean change, 0.50; SD = 0.70). Conclusions. The results of this study offer only partial support for the efficacy of modBATRAC. As in previous trials, modBATRAC facilitated increased use of the paretic arm, but unlike previous trials, it did not increase motor performance. These differences may reflect a more temporally condensed training schedule and less impaired patients.

Age-Related Differences in Lower-Limb Muscle Cross-Sectional Area and Torque Production in Boys With Duchenne Muscular Dystrophy

OBJECTIVE To examine the relationship between lower-extremity muscle cross-sectional area, muscle strength, specific torque, and age in ambulatory boys with Duchenne muscular dystrophy (DMD) compared with controls. DESIGN Observational cross-sectional study. SETTING University research setting. PARTICIPANTS Volunteer sample of boys with DMD (n=22) and healthy control boys (n=10), ages 5 through 14 years. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Maximal muscle cross-sectional area (CSA(max)) assessed by magnetic resonance imaging of quadriceps, plantarflexors (PFs) and dorsiflexors (DFs), peak isometric torque from dynamometry, and timed functional tests. RESULTS The average CSA(max) of the triceps surae muscle group was approximately 60% higher in boys with DMD compared with controls (39.1+/-13.6 cm(2) vs 24.5+/-9.3 cm(2); P=.002), while the tibialis anterior muscle showed age-appropriate increases in CSA(max). The increase in quadriceps CSA(max) was also distinctly different in boys with DMD compared with controls. Specific torque (ie, peak torque/CSA(max)) was impaired in all 3 muscles groups, with the knee extensor (KE) and PF muscles showing 4-fold, and the DF muscles 2-fold, higher values in controls compared with boys with DMD. Large age-related gains in specific torque were observed in all 3 muscle groups of control subjects, which were absent in ambulatory boys with DMD. Correlations were observed between performance on functional tasks and quadriceps and PF torque production (r=-.45 to -.57, P<.05), but not with DF strength. CONCLUSIONS Age-related changes in muscle cross-sectional area and specific torque production in lower-extremity muscles showed distinctly different patterns in the KE, PF, and DF muscles of boys with DMD compared with controls.

Magnetic Resonance Imaging and Spectroscopy Assessment of Lower Extremity Skeletal Muscles in Boys with Duchenne Muscular Dystrophy: A Multicenter Cross Sectional Study

Introduction Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that results in functional deficits. However, these functional declines are often not able to be quantified in clinical trials for DMD until after age 7. In this study, we hypothesized that 1H2O T2 derived using 1H-MRS and MRI-T2 will be sensitive to muscle involvement at a young age (5–7 years) consistent with increased inflammation and muscle damage in a large cohort of DMD subjects compared to controls. Methods MR data were acquired from 123 boys with DMD (ages 5–14 years; mean 8.6 SD 2.2 years) and 31 healthy controls (age 9.7 SD 2.3 years) using 3-Tesla MRI instruments at three institutions (University of Florida, Oregon Health & Science University, and Children’s Hospital of Philadelphia). T2-weighted multi-slice spin echo (SE) axial images and single voxel 1H-MRS were acquired from the lower leg and thigh to measure lipid fraction and 1H2O T2. Results MRI-T2, 1H2O T2, and lipid fraction were greater (p<0.05) in DMD compared to controls. In the youngest age group, DMD values were different (p<0.05) than controls for the soleus MRI-T2, 1H2O T2 and lipid fraction and vastus lateralis MRI-T2 and 1H2O T2. In the boys with DMD, MRI-T2 and lipid fraction were greater (p<0.05) in the oldest age group (11–14 years) than the youngest age group (5–6.9 years), while 1H2O T2 was lower in the oldest age group compared to the young age group. Discussion Overall, MR measures of T2 and lipid fraction revealed differences between DMD and Controls. Furthermore, MRI-T2 was greater in the older age group compared to the young age group, which was associated with higher lipid fractions. Overall, MR measures of T2 and lipid fraction show excellent sensitivity to DMD disease pathologies and potential therapeutic interventions in DMD, even in the younger boys.

Relationships of thigh muscle contractile and non-contractile tissue with function, strength, and age in boys with Duchenne muscular dystrophy

The purpose of this study was to assess the contractile and non-contractile content in thigh muscles of patients with Duchenne muscular dystrophy (DMD) and determine the relationship with functional abilities. Magnetic resonance images of the thigh were acquired in 28 boys with DMD and 10 unaffected boys. Muscle strength, timed functional tests, and the Brookes Lower Extremity scale were also assessed. Non-contractile content in the DMD group was significantly greater than in the control group for six muscles, including rectus femoris, biceps femoris-long head and adductor magnus. Non-contractile content in the total thigh musculature assessed by MRI correlated with the Brookes scale (r(s)=0.75) and supine-up test (r(s)=0.68), as well as other functional measures. An age-related specific torque increase was observed in the control group (r(s)=0.96), but not the DMD (r(s)=0.06). These findings demonstrate that MRI measures of contractile and non-contractile content can provide important information about disease progression in DMD.