A longitudinal study of disease progression in facioscapulohumeral muscular dystrophy (FSHD).

INTRODUCTION/AIMS: In preparation for clinical trials, it is important to better understand how disease burden changes over time in facioscapulohumeral muscular dystrophy (FSHD) and to assess the capability of select metrics to detect these changes. This study aims to evaluate FSHD disease progression over 1 year and to examine the sensitivity of several outcome measures in detecting changes during this interval. METHODS: We conducted a 12-month prospective observational study of 41 participants with FSHD. Participants were evaluated at baseline, 6 months, and 12 months with serial strength testing (manual muscle testing or MMT and maximum voluntary isometric contraction testing or MVICT), functional testing (FSHD-Composite Outcome Measure or FSHD-COM, FSHD Clinical Severity Score or CSS, and FSHD Evaluation Score or FES), sleep and fatigue assessments, lean body mass measurements, respiratory testing, and the FSHD-Health Index patient-reported outcome. Changes in these outcome measures were assessed over the 12-month period. Associations between changes in outcome measures and both age and sex were also examined. RESULTS: In a 12-month period, FSHD participant function remained largely stable with a mild worsening of strength, measured by MMT and standardized MVICT scores, and a mild loss in lean body mass. DISCUSSION: The abilities and disease burden of adults with FSHD are largely static over a 12-month period with participants demonstrating a mild average reduction in some measures of strength. Selection of patients, outcome measures, and trial duration should be carefully considered during the design and implementation of future clinical studies involving FSHD patients.

Acquired amusia after a right middle cerebral artery infarction - a case study.

A 62-year-old musician-MM-developed amusia after a right middle-cerebral-artery infarction. Initially, MM showed melodic deficits while discriminating pitch-related differences in melodies, musical memory problems, and impaired sensitivity to tonal structures, but normal pitch discrimination and spectral resolution thresholds, and normal cognitive and language abilities. His rhythmic processing was intact when pitch variations were removed. After 3 months, MM showed a large improvement in his sensitivity to tonality, but persistent melodic deficits and a decline in perceiving the metric structure of rhythmic sequences. We also found visual cues aided melodic processing, which is novel and beneficial for future rehabilitation practice.

Reference curves of motor function outcomes in young steroid-naïve males with Duchenne muscular dystrophy.

AIM: To investigate functional motor performance in a large cohort of young steroid-naïve males with Duchenne muscular dystrophy (DMD) and typically developing males, and to develop specific reference curves for both groups. Also, to describe associations between anthropometric values and functional motor outcomes. METHOD: Cross-sectional data of 196 steroid-naïve males with DMD aged 4 to 8 years and 497 typically developing males aged 2 years 6 months to 8 years were included. Both groups were evaluated with the time to rise from the floor test, 10-metre walk/run test, 6-minute walk test, and North Star Ambulatory Assessment. Reference curves with centiles 5%, 10%, 25%, 50%, 75%, 90%, and 95% were estimated using quantile regression. RESULTS: Males with DMD scored significantly worse on all functional motor outcomes than age-matched typically developing males (p < 0.001): 89% to 95% of the males with DMD scored below the 5th centile of the typically developing males. No or weak correlations exist between anthropometric values and functional motor outcomes. INTERPRETATION: The estimated reference curves can support consultation with families of young males with DMD and can support the evaluation of treatment for reaching motor skills and functional motor outcomes compared with typically developing males.

Milestones of progression in myotonic dystrophy type 1 and type 2.

INTRODUCTION/AIMS: Disease progression in myotonic dystrophy (DM) is marked by milestone events when functional thresholds are crossed. DM type 2 (DM2) is considered less severe than DM type 1 (DM1), but it is unknown whether this applies uniformly to all features. We compared the age-dependent risk for milestone events in DM1 and DM2 and tested for associations with age of onset and sex. METHODS: We studied a large cohort of adult participants in a national registry of DM1 and DM2. Using annual surveys from participants, we ascertained milestone events for motor involvement (use of cane, walker, ankle brace, wheelchair, or ventilatory device), systemic involvement (diabetes, pacemaker, cancer), loss of employment due to DM, and death. RESULTS: Mean follow-up of registry participants (929 DM1 and 222 DM2 patients) was 7 years. Disability and motor milestones occurred at earlier ages in DM1 than in DM2. In contrast, the risk of diabetes was higher and tended to occur earlier in DM2 (hazard ratio [HR], 0.56; P ≤ .001). In DM1, the milestone events tended to occur earlier, and life expectancy was reduced, when symptoms began at younger ages. In DM1, men were at greater risk for disability (HR, 1.34; P ≤ .01), use of ankle braces (HR, 1.41; P = .02), and diabetes (HR, 2.2; P ≤ .0001), whereas women were at greater risk for needing walkers (HR, 0.68; P = .001) or malignancy (HR, 0.66; P ≤ .01). DISCUSSION: Milestone events recorded through registries can be used to assess long-term impact of DM in large cohorts. Except for diabetes, the age-related risk of milestone events is greater in DM1 than in DM2.

Effect of Different Corticosteroid Dosing Regimens on Clinical Outcomes in Boys With Duchenne Muscular Dystrophy: A Randomized Clinical Trial.

Importance: Corticosteroids improve strength and function in boys with Duchenne muscular dystrophy. However, there is uncertainty regarding the optimum regimen and dosage. Objective: To compare efficacy and adverse effects of the 3 most frequently prescribed corticosteroid regimens in boys with Duchenne muscular dystrophy. Design, Setting, and Participants: Double-blind, parallel-group randomized clinical trial including 196 boys aged 4 to 7 years with Duchenne muscular dystrophy who had not previously been treated with corticosteroids; enrollment occurred between January 30, 2013, and September 17, 2016, at 32 clinic sites in 5 countries. The boys were assessed for 3 years (last participant visit on October 16, 2019). Interventions: Participants were randomized to daily prednisone (0.75 mg/kg) (n = 65), daily deflazacort (0.90 mg/kg) (n = 65), or intermittent prednisone (0.75 mg/kg for 10 days on and then 10 days off) (n = 66). Main Outcomes and Measures: The global primary outcome comprised 3 end points: rise from the floor velocity (in rise/seconds), forced vital capacity (in liters), and participant or parent global satisfaction with treatment measured by the Treatment Satisfaction Questionnaire for Medication (TSQM; score range, 0 to 100), each averaged across all study visits after baseline. Pairwise group comparisons used a Bonferroni-adjusted significance level of .017. Results: Among the 196 boys randomized (mean age, 5.8 years [SD, 1.0 years]), 164 (84%) completed the trial. Both daily prednisone and daily deflazacort were more effective than intermittent prednisone for the primary outcome (P < .001 for daily prednisone vs intermittent prednisone using a global test; P = .017 for daily deflazacort vs intermittent prednisone using a global test) and the daily regimens did not differ significantly (P = .38 for daily prednisone vs daily deflazacort using a global test). The between-group differences were principally attributable to rise from the floor velocity (0.06 rise/s [98.3% CI, 0.03 to 0.08 rise/s] for daily prednisone vs intermittent prednisone [P = .003]; 0.06 rise/s [98.3% CI, 0.03 to 0.09 rise/s] for daily deflazacort vs intermittent prednisone [P = .017]; and -0.004 rise/s [98.3% CI, -0.03 to 0.02 rise/s] for daily prednisone vs daily deflazacort [P = .75]). The pairwise comparisons for forced vital capacity and TSQM global satisfaction subscale score were not statistically significant. The most common adverse events were abnormal behavior (22 [34%] in the daily prednisone group, 25 [38%] in the daily deflazacort group, and 24 [36%] in the intermittent prednisone group), upper respiratory tract infection (24 [37%], 19 [29%], and 24 [36%], respectively), and vomiting (19 [29%], 17 [26%], and 15 [23%]). Conclusions and Relevance: Among patients with Duchenne muscular dystrophy, treatment with daily prednisone or daily deflazacort, compared with intermittent prednisone alternating 10 days on and 10 days off, resulted in significant improvement over 3 years in a composite outcome comprising measures of motor function, pulmonary function, and satisfaction with treatment; there was no significant difference between the 2 daily corticosteroid regimens. The findings support the use of a daily corticosteroid regimen over the intermittent prednisone regimen tested in this study as initial treatment for boys with Duchenne muscular dystrophy. Trial Registration: ClinicalTrials.gov Identifier: NCT01603407.

Ankle bracing practices in ambulatory, corticosteroid-naive boys with Duchenne muscular dystrophy.

INTRODUCTION: Loss of ambulation in Duchenne muscular dystrophy presages scoliosis, respiratory failure, and death. Strategies to maintain ankle range of motion are employed, but little evidence exists to support these approaches and limited information is available concerning current practice. METHODS: In this study we assessed baseline bracing data from 187 boys participating in a multicenter, international clinical trial. RESULTS: Ankle-foot orthoses (AFOs) were recommended for 54% of the boys, with nighttime static AFOs and nighttime dynamic AFOs utilized in 94% and 6% of these boys, respectively. Daytime static AFOs were recommended for 3 boys. Compliance with bracing recommendations was 54% for nighttime static braces and 67% for nighttime dynamic braces. DISCUSSION: The basis for the variation in recommended AFO use is unknown and requires further study. Long-term follow-up of boys may permit assessment of the effects of AFO use.

Myotonic dystrophy patient preferences in patient-reported outcome measures.

INTRODUCTION: When preparing for clinical trials in myotonic dystrophy type-1 (DM1), it is important that researchers develop and identify patient-reported outcome measures with good measurement properties. METHODS: Fifty-two DM1 patients enrolled in 2 clinical studies completed the Myotonic Dystrophy Health Index (MDHI), 36-Item Short Form Health Survey (version 2; SF-36v2), Individualized Neuromuscular Quality of Life questionnaire (INQoL), and a questionnaire comparing the relevance, usability, overall preference, and perceived responsiveness of each measure. The associations between instrument scores and physical function, genetic test results, and employment status were examined. RESULTS: The MDHI was preferred over the INQoL in 13 of 13 areas and was preferred over the SF-36v2 in 9 of 13 areas. The MDHI was the only score that was associated with participant employment status, CTG repeat length, and the 3 measurements of clinical function. DISCUSSION: The MDHI correlates well with physical function and is viewed favorably by participants in DM1 clinical studies. Muscle Nerve, 2018.

Electrical impedance myography in facioscapulohumeral muscular dystrophy: A 1-year follow-up study.

INTRODUCTION: Electrical impedance myography (EIM) is a noninvasive technique for measuring muscle composition and a potential physiological biomarker for facioscapulohumeral muscular dystrophy (FSHD). METHODS: Thirty-two participants with genetically confirmed and clinically affected FSHD underwent EIM in 7 muscles bilaterally. Correlations between EIM and baseline clinical measures were used to select EIM variables of interest in FSHD, and EIM and clinical measures were followed for 1 year. RESULTS: There were no significant changes in the EIM variables. Although 50-kHZ reactance correlated the strongest with clinical measures at baseline, the 50-211-kHZ phase ratio demonstrated lower within-subject 12-month variability, potentially offering sample size savings for FSHD clinical trial planning. DISCUSSION: EIM did not identify significant disease progression over 12 months. It is currently unclear whether this is because of limitations of the technology or the slow rate of disease progression in this cohort of FSHD patients over this period of time. Muscle Nerve 58: 213-218, 2018.

Facioscapulohumeral muscular dystrophy functional composite outcome measure.

INTRODUCTION: We developed an evaluator-administered functional facioscapulohumeral muscular dystrophy composite outcome measure (FSHD-COM) comprising patient-identified areas of functional burden for future clinical trials. METHODS: We performed a prospective observational study of 41 patients with FSHD at 2 sites. The FSHD-COM includes functional assessment of the legs, shoulders and arms, trunk, hands, and balance/mobility. We determined the test-retest reliability and convergent validity compared to established FSHD disease metrics. RESULTS: The FSHD-COM demonstrated excellent test-retest reliability (intraclass correlation coefficient [ICC] 0.96; subscale ICC range, 0.90-0.94). Cross-sectional associations between the FSHD-COM and disease duration, clinical severity, and strength were moderate to strong (Pearson correlation coefficient range |0.51-0.92|). DISCUSSION: The FSHD-COM is a disease-relevant, functional composite outcome measure suitable for future FSHD clinical trials that shows excellent test-retest reliability and cross-sectional associations to disease measures. Future directions include determining multisite reliability, sensitivity to change, and the minimal clinically important change in the FSHD-COM. Muscle Nerve, 2018.

Quantitative Evaluation of Lower Extremity Joint Contractures in Spinal Muscular Atrophy: Implications for Motor Function.

PURPOSE: To quantitatively describe passive lower extremity range of motion in participants with spinal muscular atrophy (SMA) types 2 and 3, and to establish preliminary thresholds to identify individuals at risk for performing poorly on disease-specific motor function outcome measures. METHODS: Eighty participants with SMA types 2 and 3, enrolled in an international multicenter natural history study, were evaluated with lower extremity range of motion testing and the Hammersmith Functional Motor Scale-Expanded. RESULTS: A hip extension joint angle of -7.5° or less for SMA type 2 and 0° or less for SMA type 3 identified diminished motor ability with good sensitivity. For knee extension, a joint angle of -9.0° or less for SMA type 2 or 0° or less for SMA type 3 was similarly sensitive. CONCLUSIONS: Minimal hip and knee joint contractures were associated with diminished motor ability. Clinical trial designs should consider the effect of contractures on motor function.

Electrical impedance myography in facioscapulohumeral muscular dystrophy.

INTRODUCTION: In this study we determined the reliability and validity of electrical impedance myography (EIM) in facioscapulohumeral muscular dystrophy (FSHD). METHODS: We performed a prospective study of EIM on 16 bilateral limb and trunk muscles in 35 genetically defined and clinically affected FSHD patients (reliability testing on 18 patients). Summary scores based on body region were derived. Reactance and phase (50 and 100 kHz) were compared with measures of strength, FSHD disease severity, and functional outcomes. RESULTS: Participants were mostly men, mean age 53.0 years, and included a full range of severity. Limb and trunk muscles showed good to excellent reliability [intraclass correlation coefficients (ICC) 0.72-0.99]. Summary scores for the arm, leg, and trunk showed excellent reliability (ICC 0.89-0.98). Reactance was the most sensitive EIM parameter to a broad range of FSHD disease metrics. CONCLUSIONS: EIM is a reliable measure of muscle composition in FSHD that offers the possibility to serially evaluate affected muscles. Muscle Nerve 54: 696-701, 2016.

Myotonic dystrophy health index: Correlations with clinical tests and patient function.

INTRODUCTION: The Myotonic Dystrophy Health Index (MDHI) is a disease-specific patient-reported outcome measure. Here, we examine the associations between the MDHI and other measures of disease burden in a cohort of individuals with myotonic dystrophy type-1 (DM1). METHODS: We conducted a cross-sectional study of 70 patients with DM1. We examined the associations between MDHI total and subscale scores and scores from other clinical tests. Participants completed assessments of strength, myotonia, motor and respiratory function, ambulation, and body composition. Participants also provided blood samples, underwent physician evaluations, and completed other patient-reported outcome measures. RESULTS: MDHI total and subscale scores were strongly associated with muscle strength, myotonia, motor function, and other clinical measures. CONCLUSIONS: Patient-reported health status, as measured by the MDHI, is associated with alternative measures of clinical health. These results support the use of the MDHI as a valid tool to measure disease burden in DM1 patients.

Rasch analysis of the Pediatric Evaluation of Disability Inventory-computer adaptive test (PEDI-CAT) item bank for children and young adults with spinal muscular atrophy.

INTRODUCTION: In this study we evaluated the suitability of a caregiver-reported functional measure, the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT), for children and young adults with spinal muscular atrophy (SMA). METHODS: PEDI-CAT Mobility and Daily Activities domain item banks were administered to 58 caregivers of children and young adults with SMA. Rasch analysis was used to evaluate test properties across SMA types. RESULTS: Unidimensional content for each domain was confirmed. The PEDI-CAT was most informative for type III SMA, with ability levels distributed close to 0.0 logits in both domains. It was less informative for types I and II SMA, especially for mobility skills. Item and person abilities were not distributed evenly across all types. CONCLUSIONS: The PEDI-CAT may be used to measure functional performance in SMA, but additional items are needed to identify small changes in function and best represent the abilities of all types of SMA. Muscle Nerve 54: 1097-1107, 2016.

Spinal muscular atrophy functional composite score: A functional measure in spinal muscular atrophy.

INTRODUCTION: With clinical trials underway, our objective was to construct a composite score of global function that could discriminate among people with spinal muscular atrophy (SMA). METHODS: Data were collected from 126 participants with SMA types 2 and 3. Scores from the Hammersmith Functional Motor Scale-Expanded and Upper Limb Module were expressed as a percentage of the maximum score and 6-minute walk test as percent of predicted normal distance. A principal component analysis was performed on the correlation matrix for the 3 percentage scores. RESULTS: The first principal component yielded a composite score with approximately equal weighting of the 3 components and accounted for 82% of the total variability. The SMA functional composite score, an unweighted average of the 3 individual percentage scores, correlated almost perfectly with the first principal component. CONCLUSIONS: This combination of measures broadens the spectrum of ability that can be quantified in type 2 and 3 SMA patients.

Myotonic Dystrophy Health Index: initial evaluation of a disease-specific outcome measure.

INTRODUCTION: In preparation for clinical trials we examine the validity, reliability, and patient understanding of the Myotonic Dystrophy Health Index (MDHI). METHODS: Initially we partnered with 278 myotonic dystrophy type-1 (DM1) patients and identified the most relevant questions for the MDHI. Next, we used factor analysis, patient interviews, and test-retest reliability assessments to refine and evaluate the instrument. Lastly, we determined the capability of the MDHI to differentiate between known groups of DM1 participants. RESULTS: Questions in the final MDHI represent 17 areas of DM1 health. The internal consistency was acceptable in all subscales. The MDHI had a high test-retest reliability (ICC = 0.95) and differentiated between DM1 patient groups with different disease severities. CONCLUSIONS: Initial evaluation of the MDHI provides evidence that it is valid and reliable as an outcome measure for assessing patient-reported health. These results suggest that important aspects of DM1 health may be measured effectively using the MDHI.

Factors Associated With Early Motor Function Trajectories in DMD After Glucocorticoid Initiation: Post Hoc Analysis of the FOR-DMD Trial.

BACKGROUND AND OBJECTIVES: Clinical trials in Duchenne muscular dystrophy (DMD) require 3-6 months of stable glucocorticoids, and the primary outcome is explored at 48-52 weeks. The factors that influence the clinical outcome assessment (COA) trajectories soon after glucocorticoid initiation are relevant for the design and analysis of clinical trials of novel drugs. We describe early COA trajectories, associated factors, and the time from glucocorticoid initiation to COA peak. METHODS: This was a prospective 18-month analysis of the Finding the Optimum Corticosteroid Regimen for Duchenne Muscular Dystrophy study. Four COAs were investigated: rise from supine velocity (RFV), 10-meter walk/run velocity (10MWRV), North Star Ambulatory Assessment (NSAA) total score, and 6-minute walk test distance (6MWT). The relationships of baseline age (4-5 vs 6-7 years), COA baseline performance, genotype, and glucocorticoid regimen (daily vs intermittent) with the COA trajectories were evaluated using linear mixed-effects models. RESULTS: One hundred ninety-six glucocorticoid-naïve boys with DMD aged 4-7 years were enrolled. The mean age at baseline was 5.9 ± 1.0 years, 66% (n = 130) were on daily regimens, 55% (n = 107) showed a 6MWT distance >330 metres; 41% (n = 78) showed RFV >0.2 rise/s; 76% (n = 149) showed 10MWRV >0.142 10m/s, and 41.0% (n = 79) showed NSAA total score >22 points. Mean COA trajectories differed by age at glucocorticoid initiation (p < 0.01 for RFV, 10MWRV, and NSAA; p < 0.05 for 6MWT) and regimen (p < 0.01 for RFV, 10MWRV, and NSAA). Boys younger than 6 years reached their peak performance 12-18 months after glucocorticoid initiation. Boys aged 6 years or older on a daily regimen peaked between months 9 and 12 and those on an intermittent regimen by 9 months. The baseline COA performance was associated with the NSAA (p < 0.01) and the 6MWT trajectory in boys younger than 6 years on a daily regimen (p < 0.01). Differences in the mean trajectories by genotype were not significant. DISCUSSION: Glucocorticoid regimen, age, duration of glucocorticoid exposure, and baseline COA performance need to be considered in the design and analysis of clinical trials in young boys with DMD.

Assessing Bulbar Function in Spinal Muscular Atrophy Using Patient-Reported Outcomes.

BACKGROUND: Novel Spinal Muscular Atrophy (SMA) treatments have demonstrated improvements on motor measures that are clearly distinct from the natural history of progressive decline. Comparable measures are needed to monitor bulbar function, which is affected in severe SMA. OBJECTIVE: To assess bulbar function with patient-reported outcome measures (PROs) and determine their relationships with clinical characteristics. METHODS: We recruited 47 non-ambulatory participants (mean (SD) age = 29.8 (13.7) years, range = 10.3-73.2) with SMA. PROs including Voice Handicap Index (VHI) and Eating Assessment Tool-10 (EAT-10) were collected alongside clinical characteristics and standardized motor assessments. Associations were assessed using Spearman correlation coefficients and group comparisons were performed using Wilcoxon rank sum tests. RESULTS: A majority of the 47 participants were SMA type 2 (70.2%), non-sitters (78.7%), 3 copies of SMN2 (77.5%), and using respiratory support (66.0%). A majority (94%) reported voice issues primarily in 8/30 VHI questions. Problems included: difficulty understanding me in a noisy room (87.2%); difficult for people to hear me (74.5%); and people ask me to repeat when speaking face-to-face (72.3%). A majority (85.1%) reported swallowing issues primarily in 3/10 EAT-10 questions: swallowing pills (68.1%); food sticks to my throat (66.0%); and swallowing solids (61.7%). The two PROs were moderately associated (rs = 0.66). CONCLUSIONS: Weaker individuals with SMA experience bulbar problems including difficulties with voice and swallowing. Further refinement and assessment of functional bulbar scales will help determine their relevance and responsiveness to changes in SMA. Additional study is needed to quantify bulbar changes caused by SMA and their response to disease-modifying treatments.

Lean tissue mass measurements by dual-energy X-ray absorptiometry and associations with strength and functional outcome measures in facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive disease of skeletal muscle. Dual energy X-ray absorptiometry (DEXA) is a widely available, cost-effective and sensitive technique for measuring whole body and regional lean tissue mass and has been used in prior clinical trials in neuromuscular diseases. The Clinical Trial Readiness to Solve Barriers to Drug Development in FSHD (ReSolve) study is a prospective, longitudinal, observational multisite study. We obtained concurrent DEXA scans and functional outcome measurements in 185 patients with FSHD at the baseline visit. We determined the associations between lean tissue mass in the upper and lower extremities and corresponding clinical outcome measures. There were moderate correlations between upper and lower extremity lean tissue mass and their corresponding strengths and function. Lean tissue mass obtained by DEXA scan may be useful as a biomarker in future clinical trials in FSHD.

A quantitative measure of handgrip myotonia in non-dystrophic myotonia.

INTRODUCTION: Non-dystrophic myotonia (NDM) is characterized by myotonia without muscle wasting. A standardized quantitative myotonia assessment (QMA) is important for clinical trials. METHODS: Myotonia was assessed in 91 individuals enrolled in a natural history study using a commercially available computerized handgrip myometer and automated software. Average peak force and 90% to 5% relaxation times were compared with historical normal controls studied with identical methods. RESULTS: Thirty subjects had chloride channel mutations, 31 had sodium channel mutations, 6 had DM2 mutations, and 24 had no identified mutation. Chloride channel mutations were associated with prolonged first handgrip relaxation times and warm-up on subsequent handgrips. Sodium channel mutations were associated with prolonged first handgrip relaxation times and paradoxical myotonia or warm-up, depending on underlying mutations. DM2 subjects had normal relaxation times but decreased peak force. Sample size estimates are provided for clinical trial planning. CONCLUSION: QMA is an automated, non-invasive technique for evaluating myotonia in NDM.

The effect of loudness on the reverberance of music: reverberance prediction using loudness models.

This study examines the auditory attribute that describes the perceived amount of reverberation, known as "reverberance." Listening experiments were performed using two signals commonly heard in auditoria: excerpts of orchestral music and western classical singing. Listeners adjusted the decay rate of room impulse responses prior to convolution with these signals, so as to match the reverberance of each stimulus to that of a reference stimulus. The analysis examines the hypothesis that reverberance is related to the loudness decay rate of the underlying room impulse response. This hypothesis is tested using computational models of time varying or dynamic loudness, from which parameters analogous to conventional reverberation parameters (early decay time and reverberation time) are derived. The results show that listening level significantly affects reverberance, and that the loudness-based parameters outperform related conventional parameters. Results support the proposed relationship between reverberance and the computationally predicted loudness decay function of sound in rooms.