BACKGROUND Electrical impedance myography (EIM) and quantitative ultrasound (QUS) are two non-invasive, painless, and effort-independent approaches for assessing neuromuscular disease. Both techniques have potential to serve as useful biomarkers in clinical trials in Duchenne muscular dystrophy (DMD). However, their comparative sensitivity to disease status and how they relate to one another is unknown. METHODS We performed a cross-sectional analysis of EIM and QUS in 24 healthy boys and 24 with DMD, aged 2-14 years with trained research assistants performing all measurements. Three upper and three lower extremity muscles were studied unilaterally in each child and the data averaged for each individual. RESULTS Both EIM and QUS differentiated healthy boys from those with DMD (p<0.001 for both). QUS values correlated with age in DMD boys (rho=0.45, p=0.029), whereas EIM did not (rho=−0.31, p=0.14). However, EIM phase correlated with age in healthy boys (rho=0.51, p= 0.012) whereas QUS did not (rho =−0.021, p =0.92). In DMD boys, EIM phase correlated with the North Star Ambulatory Assessment (EIM: rho=0.65, p=0.022); QUS showed a near-significant association (rho=−0.56, p=0.060). The two technologies trended toward a moderate correlation with one another in the DMD cohort but not in the healthy group (rho=−0.40, p=0.054, rho=−0.32, p=0.13, respectively). CONCLUSIONS EIM and QUS are complementary modalities for the assessment of boys with DMD; further study and application of these two modalities alone or in combination in a longitudinal fashion is warranted.

Introduction Muscle pathology in Duchenne muscular dystrophy (DMD) can be quantified using ultrasound by measuring either the amplitudes of sound-waves scattered back from the tissue [quantitative backscatter analysis (QBA)] or by measuring these backscattered amplitudes after compression into grayscale levels obtained from the images (GSL). Methods We measured and compared QBA and GSL from 6 muscles of 25 boys with DMD and 25 healthy subjects, aged 2–14 years, with age and, in DMD, with function (North Star Ambulatory Assessment). Results Both QBA and GSL were measured reliably (intraclass correlation ≥ 0.87) and were higher in DMD than controls (P<0.0001). In DMD, average QBA and GSL measured from superficial regions of muscle increased (rho ≥ 0.47, P < 0.05) with both higher age and worse function; in contrast, GSL measured from whole regions of muscle did not. Discussion QBA and GSL measured from superficial regions of muscle can similarly quantify muscle pathology in DMD.

Purpose Impaired consciousness in epileptic seizures has a major negative impact on patient quality of life. Prior work on epileptic unconsciousness has mainly used retrospective and nonstandardized methods. Our goal was to validate and to obtain initial data using a standardized prospective testing battery. Methods The responsiveness in epilepsy scale (RES) was used on 52 patients during continuous video/EEG monitoring. RES begins with higher-level questions and commands, and switches adaptively to more basic sensorimotor responses depending on patient performance. RES continues after seizures and includes postictal memory testing. Scoring was conducted based on video review. Key Findings Testing on standardized seizure simulations yielded good intra-rater and inter-rater reliability. We captured 59 seizures from 18 patients (35% of participants) during 1420 hours of RES monitoring. RES impairment was greatest during and after tonic-clonic seizures, less in partial seizures, and minimal in auras and subclinical seizures. In partial seizures, ictal RES impairment was significantly greater if EEG changes were present. Maximum RES impairment (lowest ictal score) was also significantly correlated with long postictal recovery time, and poor postictal memory. Significance We found that prospective testing of responsiveness during seizures is feasible and reliable. RES impairment was related to EEG changes during seizures, as well as to postictal memory deficits and recovery time. With a larger patient sample it is hoped that this approach can identify brain networks underlying specific components of impaired consciousness in seizures. This may allow the development of improved treatments targeted at preventing dysfunction in these networks.

BACKGROUND Compared to individual parameters, composite biomarkers may provide a more effective means for monitoring disease progression and the effects of therapy in clinical trials than single measures. In this study, we built composite biomarkers for use in Duchenne muscular dystrophy (DMD) by combining values from two objective measures of disease severity: electrical impedance myography (EIM) and quantitative ultrasound (QUS) and evaluating how well they correlated to standard functional measures. METHODS Utilizing data from an ongoing study of EIM and QUS in 31 DMD and 26 healthy boys aged 2–14 years, we combined data sets by first creating z-scores based on the normal subject data and then using simple mathematical operations (addition and multiplication) to create composite measures. These composite scores were then correlated to age and standard measures of function including the six-minute walk test, the North Star Ambulatory Assessment (NSAA), and handheld dynamometry. RESULTS Combining data sets resulted in stronger correlations with all four outcomes than for either EIM or QUS alone in six of eight instances. These improvements reached statistical significance (p < 0.05) in several cases. For example, the correlation coefficient for the composite measure with the NSAA was 0.79 but was only 0.66 and 0.67 (respectively) for GSL and EIM separately. CONCLUSIONS Arithmetically derived composite scores can provide stronger correlations to functional measures than isolated biomarkers. Longitudinal study of such composite markers in DMD clinical trials is warranted.

Objectives The purpose of this study was to investigate the ability of quantitative ultrasound (US) using edge detection analysis to assess patients with Duchenne muscular dystrophy (DMD). Methods After Institutional Review Board approval, US examinations with fixed technical parameters were performed unilaterally in 6 muscles (biceps, deltoid, wrist flexors, quadriceps, medial gastrocnemius, and tibialis anterior) in 19 boys with DMD and 21 age-matched control participants. The muscles of interest were outlined by a tracing tool, and the upper third of the muscle was used for analysis. Edge detection values for each muscle were quantified by the Canny edge detection algorithm and then normalized to the number of edge pixels in the muscle region. The edge detection values were extracted at multiple sensitivity thresholds (0.01–0.99) to determine the optimal threshold for distinguishing DMD from normal. Area under the receiver operating curve values were generated for each muscle and averaged across the 6 muscles. Results The average age in the DMD group was 8.8 years (range, 3.0–14.3 years), and the average age in the control group was 8.7 years (range, 3.4–13.5 years). For edge detection, a Canny threshold of 0.05 provided the best discrimination between DMD and normal (area under the curve, 0.96; 95% confidence interval, 0.84–1.00). According to a Mann-Whitney test, edge detection values were significantly different between DMD and controls (P < .0001). Conclusions Quantitative US imaging using edge detection can distinguish patients with DMD from healthy controls at low Canny thresholds, at which discrimination of small structures is best. Edge detection by itself or in combination with other tests can potentially serve as a useful biomarker of disease progression and effectiveness of therapy in muscle disorders.

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