Introduction: Data is currently lacking anchoring a 30-meter longitudinal change in walking ability by 6-minute walk test (6MWT) in Duchenne muscular dystrophy as a minimal clinically important difference and “clinically meaningful” person-reported outcomes (PROs) at differing levels of ambulatory ability. Methods: We describe correlation between measures, 1-year change in measures, and correlation of 1-year changes between measures for the six-minute walk test (6MWT), 10-meter run/walk velocity, PedsQL and POSNA Pediatric Outcomes Data Collection Instrument (PODCI) in 24 4-12 year old. ambulatory DMD and 36 typical controls, and determine if minimal clinically important differences (MCID) of PROs contribute to different estimates of 6-minute walk distance (6MWD) change at differing levels of ability. Results: PedsQL total and physical function and PODCI global, transfer/mobility and sports/physical function PROs demonstrated significant differences between DMD and controls (p<0.00001). In DMD, 6MWD and 10-meter run/walk velocity were correlated with PODCI domain scores, with the transfer/mobility scale showing the strongest relationship (r=0.79 and r=0.76). In DMD, 6MWD distance and 10-meter run/walk velocity weakly correlated with PedsQL domain scores. In DMD, 6MWD, 10-meter run/walk velocity, and PODCI global and transfer and basic mobility demonstrated significant one-year change and exceeded the amount of change representing MCID. In DMD, 6MWD change highly correlated with change in PODCI global and PODCI transfer/mobility scores (r=0.76 and r=0.93). PODCI global and PODCI transfer/mobility scales provided the best estimates of 6MWT performance. A “meaningful” 4.5 point change in a low PODCI transfer / basic mobility score of 30 to 34.5 was associated with a 5.6m 6MWD change from 150.3 to 155.9m. At PODCI levels closer to normative levels for healthy controls, the change in 6MWD distance associated with a “meaningful” change in PODCI scores was almost 46m. Discussion: At lower levels of function, smaller increases in 6MWD result in meaningful change in quality of life (QoL) instrument scores. At higher levels of function, larger increases may be necessary to achieve the same QoL change score.

The steep adolescent decline in the slow wave (delta, 1-4 Hz) electroencephalogram (EEG) of nonrapid eye movement (NREM) sleep is a dramatic maturational change in brain electrophysiology thought to be driven by cortical synaptic pruning. A perennial question is whether this change in brain electrophysiology is related to sexual maturation. Applying Gompertz growth models to longitudinal data spanning ages 9-18 y, we found that the timing of the delta decline was significantly (P < 0.0001) linked to timing of pubertal maturation. This timing relation remained significant when sex differences in the timing of the delta decline were statistically controlled. Sex differences and the relation to the timing of puberty jointly explained 67% of the between-subject variance in the timing of the delta decline. These data provide a demonstration of a temporal relation between puberty and an electrophysiological marker of adolescent brain development. They can guide research into whether the neuroendocrine events of puberty are mechanistically linked to cortical maturation or whether, instead, the two maturational processes are parallel but independent programs of human ontogenesis. n an ongoing longitudinal study of adolescent sleep EEG, we identified the age range 12-16.5 y as a critical period of late brain maturation (1). Centrally recorded slow wave (delta, 1-4 Hz) EEG power in nonrapid eye movement (NREM) sleep declines by >60% in this 4.5-y range. We (2) and others (3,4) have proposed that the decline in delta power reflects the cortical synaptic pruning discovered by Huttenlocher (5). The decline in delta power also bears importantly on the physiology of sleep regulation because NREM slow wave EEG seems to reflect a recuperative process (6, 7); it increases with prior waking duration and declines across the night.A recurrent question is whether the dramatic changes in sleep electrophysiology during adolescence are related to the concurrent physical changes of puberty. Previous studies have found lower levels of visually scored slow wave sleep (8) or delta power (3) in more sexually mature subjects, but these studies did not control for age. In 2006, we analyzed the data then available from our longitudinal study to examine sleep EEG changes in relation to both age and pubertal maturation (9). We reported a strong relation between the rate of the delta decline and the rate of progression through the Tanner stages of pubertal maturation. However, both rates were strongly related to age. When age was statistically controlled, the relation between delta power and Tanner stage became nonsignificant.Our 2006 article included data only from ages 9-11 and 12-14 y and evaluated the rate of delta decline but not its timing. We are now able to analyze the timing of the relation between the decline in NREM delta EEG power and pubertal maturation in an expanded longitudinal dataset, which now includes ages 9-18 y. These analyses show a highly significant relation between the timing of the delta decline and the timing of pubert...

Introduction A depth-ranging sensor (Kinect) based upper extremity motion analysis system was applied to determine the spectrum of reachable workspace encountered in facioscapulohumeral muscular dystrophy (FSHD). Methods Reachable workspaces were obtained from 22 individuals with FSHD and 24 age- and height-matched healthy controls. To allow comparison, total and quadrant reachable workspace relative surface areas (RSA) were obtained by normalizing the acquired reachable workspace by each individual’s arm length. Results Significantly contracted reachable workspace and reduced RSAs were noted for the FSHD cohort compared to controls (0.473±0.188 vs. 0.747±0.082; P<0.0001). With worsening upper extremity function as categorized by the FSHD evaluation subscale II+III, the upper quadrant RSAs decreased progressively, while the lower quadrant RSAs were relatively preserved. There were no side-to-side differences in reachable workspace based on hand-dominance. Discussion This study demonstrates the feasibility and potential of using an innovative Kinect-based reachable workspace outcome measure in FSHD.

These declines indicate that the intensity of the homeostatic or restorative processes at the beginning of sleep diminished across adolescence. We propose that this change in sleep regulation is caused by the synaptic pruning that occurs during adolescent brain maturation.

We maintain our interpretation that the adolescent decline in EEG power reflects a widespread brain reorganization driven by synaptic pruning. The late decline in frontally recorded delta power indicates that plasticity is maintained in these circuits until a later age. Although delta and theta have similar homeostatic properties, they have different age and topographic patterns that imply different functional correlates.