Updated consensus guidelines on the management of Phelan-McDermid syndrome.

Phelan-McDermid syndrome (PMS) is a genetic condition caused by SHANK3 haploinsufficiency and characterized by a wide range of neurodevelopmental and systemic manifestations. The first practice parameters for assessment and monitoring in individuals with PMS were published in 2014; recently, knowledge about PMS has grown significantly based on data from longitudinal phenotyping studies and large-scale genotype-phenotype investigations. The objective of these updated clinical management guidelines was to: (1) reflect the latest in knowledge in PMS and (2) provide guidance for clinicians, researchers, and the general community. A taskforce was established with clinical experts in PMS and representatives from the parent community. Experts joined subgroups based on their areas of specialty, including genetics, neurology, neurodevelopment, gastroenterology, primary care, physiatry, nephrology, endocrinology, cardiology, gynecology, and dentistry. Taskforce members convened regularly between 2021 and 2022 and produced specialty-specific guidelines based on iterative feedback and discussion. Taskforce leaders then established consensus within their respective specialty group and harmonized the guidelines. The knowledge gained over the past decade allows for improved guidelines to assess and monitor individuals with PMS. Since there is limited evidence specific to PMS, intervention mostly follows general guidelines for treating individuals with developmental disorders. Significant evidence has been amassed to guide the management of comorbid neuropsychiatric conditions in PMS, albeit mainly from caregiver report and the experience of clinical experts. These updated consensus guidelines on the management of PMS represent an advance for the field and will improve care in the community. Several areas for future research are also highlighted and will contribute to subsequent updates with more refined and specific recommendations as new knowledge accumulates.

A scoping review of methods used in musculoskeletal soft tissue and nerve shear wave elastography studies.

This scoping review of shear wave elastography (SWE) articles in musculoskeletal soft tissue and nerve research demonstrates methodological heterogeneity resulting from a lack of standardized data collection and reporting requirements. Seven literature databases were searched for original articles published in English from 2004-2020 that examine human skeletal muscles, tendons, and nerves in vivo. Although 5,868 records were initially identified, only 375 reports met inclusion criteria. Of the 375 articles, 260 examined 89 unique muscles, 94 examined 14 unique tendons, and 43 examined 8 unique nerves. Cohorts were often small (n = 11-20) and young (mean = 20-29 years), and participants were typically tested in the prone position. Regarding equipment, a variety of ultrasound systems (n = 11), ultrasound models (n = 18), and transducers (n = 19) were identified. Only 11% of articles contained information on the use of electromyography to confirm absence of muscle activity, and only 8% reported measurement depth. Since musculoskeletal soft tissue and nerve stiffness can vary significantly based on data collection methods, it is essential to standardize SWE collection and reporting procedures. This will allow SWE to serve as a valid and reproducible tool for assessing tissue pathology, disease progression, and response to intervention within a variety of musculoskeletal and nerve-related disorders.

Botulinum Toxin A for Chronic Exertional Compartment Syndrome Evaluated With Shear Wave Elastography: A Case Report.

ABSTRACT: This case presentation offers supportive evidence that shear wave elastography may provide an alternative method of diagnosis of chronic exertional compartment syndrome (CECS). A 39-year-old female runner presented with bilateral anterior shin pain on exertion. She initially underwent compartmental pressure testing confirming the diagnosis of CECS but declined fasciotomy. When her symptoms recurred, she was referred for botulinum toxin therapy. Shear wave muscle elastography was performed in the bilateral anterior and lateral compartments following symptom provocation treadmill testing and compared with 2 control subjects. At 6 weeks and 7 months after onabotulinumtoxinA injections, she was asymptomatic, and elastography measurements revealed a reduction in muscle stiffness from initial treadmill testing.

Diagnostic Imaging of A2 Pulley Injuries: A Review of the Literature.

Injury to the A2 pulley is caused by high eccentric forces on the flexor-tendon-pulley system. Accurate diagnosis is necessary to identify the most appropriate treatment options. This review summarizes the literature with respect to using ultrasound (US) to diagnose A2 pulley injuries, compares ultrasound to magnetic resonance imaging and computed tomography, and identifies current knowledge gaps. The results suggest that US should be used as the primary imaging modality given high accuracy, relatively low cost, ease of access, and dynamic imaging capabilities. Manual resistance is beneficial to accentuate bowstringing, but further research is needed to determine best positioning for evaluation.

Systematic Review: Recommendations for Rehabilitation in ASD and ID From Clinical Practice Guidelines.

OBJECTIVE: To identify and summarize clinical practice guidelines for autism spectrum disorder (ASD) and intellectual disability (ID) for the Package of Interventions for Rehabilitation for the World Health Organization (WHO). DATA SOURCES: Academic databases, Google Scholar, guideline databases, and professional society websites were searched using the general criteria "ASD/ID" AND "rehabilitation" AND "guideline," restricted to English-only guidelines. STUDY SELECTION: Work group members independently screened titles and abstracts (1952 ASD; 1027 ID) and excluded articles if not (1) a guideline; (2) about rehabilitation; (3) published since 2008; or (4) about ASD/ID. Full-text screening (29 ASD; 5 ID) involved 3 additional exclusion criteria: (1) contained conflict of interest; (2) lacked information on strength of recommendation; or (3) failed the Appraisal of Guidelines for Research and Evaluation II instrument. Six guidelines (4 ASD: 2 on youth, 1 on adults, 1 on all ages; 2 ID: 1 on challenging behaviors, 1 on mental health) resulted. DATA EXTRACTION: Work group members extracted 524 recommendations (386 ASD; 138 ID) from the guidelines including the level of evidence, diagnostic and age group, recommendation type (assessment, intervention, service), target, and valence. DATA SYNTHESIS: Of the 270 intervention recommendations (212 ASD; 58 ID), only 36 for ASD and 47 for ID were empirically based. Most comprised biomedical (23%), pharmacologic (29%), and psychosocial (21%) interventions for ASD and behavioral (14%), pharmacologic (29%), and psychological (14%) interventions for ID. Intervention recommendations primarily targeted coexisting conditions (56% ASD; 93% ID), whereas core symptoms received much less attention (26% ASD). CONCLUSIONS: Clinical practice guidelines reviewed for ASD and ID primarily contained recommendations based on expert opinion, with the plurality of recommendations relating to pharmacologic treatment. Vital next steps include identifying relevant interventions for inclusion in the WHO Package and continuing to conduct rigorous intervention research, particularly on core symptoms of these conditions, to extend recommendations for high-quality guidelines.

Patterns of delay in early gross motor and expressive language milestone attainment in probands with genetic conditions versus idiopathic ASD from SFARI registries.

BACKGROUND: Recent large-scale initiatives have led to systematically collected phenotypic data for several rare genetic conditions implicated in autism spectrum disorder (ASD). The onset of developmentally expected skills (e.g. walking, talking) serve as readily quantifiable aspects of the behavioral phenotype. This study's aims were: (a) describe the distribution of ages of attainment of gross motor and expressive language milestones in several rare genetic conditions, and (b) characterize the likelihood of delays in these conditions compared with idiopathic ASD. METHODS: Participants aged 3 years and older were drawn from two Simons Foundation Autism Research Initiative registries that employed consistent phenotyping protocols. Inclusion criteria were a confirmed genetic diagnosis of one of 16 genetic conditions (Simons Searchlight) or absence of known pathogenic genetic findings in individuals with ASD (SPARK). Parent-reported age of acquisition of three gross motor and two expressive language milestones was described and categorized as on-time or delayed, relative to normative expectations. RESULTS: Developmental milestone profiles of probands with genetic conditions were marked by extensive delays (including nonattainment), with highest severity in single gene conditions and more delays than idiopathic ASD in motor skills. Compared with idiopathic ASD, the median odds of delay among the genetic groups were higher by 8.3 times (IQR 5.8-16.3) for sitting, 12.4 times (IQR 5.3-19.5) for crawling, 26.8 times (IQR 7.7-41.1) for walking, 2.7 times (IQR 1.7-5.5) for single words, and 5.7 times (IQR 2.7-18.3) for combined words. CONCLUSIONS: Delays in developmental milestones, particularly in gross motor skills, are frequent and may be among the earliest indicators of differentially affected developmental processes in specific genetically defined conditions associated with ASD, as compared with those with clinical diagnoses of idiopathic ASD. The possibility of different developmental pathways leading to ASD-associated phenotypes should be considered when deciding how to employ specific genetic conditions as models for ASD.

Rhythmic auditory stimuli modulate movement recovery in response to perturbation during locomotion.

The capacity to recover after a perturbation is a well-known intrinsic property of physiological systems, including the locomotor system, and can be termed 'resilience'. Despite an abundance of metrics proposed to measure the complex dynamics of bipedal locomotion, analytical tools for quantifying resilience are lacking. Here, we introduce a novel method to directly quantify resilience to perturbations during locomotion. We examined the extent to which synchronizing stepping with two different temporal structured auditory stimuli (periodic and 1/f structure) during walking modulates resilience to a large unexpected perturbation. Recovery time after perturbation was calculated from the horizontal velocity of the body's center of mass. Our results indicate that synchronizing stepping with a 1/f stimulus elicited greater resilience to mechanical perturbations during walking compared with the periodic stimulus (3.3 s faster). Our proposed method may help to gain a comprehensive understanding of movement recovery behavior of humans and other animals in their ecological contexts.

Characterizing upper limb function in the context of activities of daily living in CLN3 disease.

In CLN3 disease, impairments in motor function are frequently reported to have later onset compared to visual and cognitive decline, but upper limb motor function has yet to be explored in this population. In a cohort of 22 individuals with CLN3, we used a novel application of multiple measures to (1) characterize motor function, particularly of the upper limbs, in activities of daily living (ADLs), and (2) explore associations between motor function and age as well as visual ability, disease severity, and cognitive function, as evaluated by the Unified Batten Disease Rating Scale (UBDRS), a validated CLN3 disease measure. ADLs that required coordination, speed, and fine motor control were particularly challenging for children with CLN3 based on item-level performance across direct assessments (Jebsen-Taylor Hand Function Test [JTHFT] and MyoSet Tools) and caregiver reports (Pediatric Evaluation of Disability Inventory-Computer Adaptive Testing [PEDI-CAT] and Patient-Reported Outcomes Measurement Information System [PROMIS] Pediatric Upper Extremity). Poorer visual ability, disease severity, and cognitive function were associated with worse performance on these measures, whereas age had limited impact. These findings support the need for children with CLN3 to receive skilled clinical evaluation and treatment tailored to their individual needs, particularly in the context of ADLs, as their symptom profile progresses.

Postural control may drive the development of other domains in infancy.

BACKGROUND: To examine differences in sitting posture in infants at low- and high-risk for autism spectrum disorder and to establish the relationship between sitting postural control and other developmental domains. METHODS: A total of 19 infants participated in the study. Eight infants at high-risk and 11 infants at low-risk for autism spectrum disorder. Sitting posture at 6 months was evaluated using a force platform while center of pressure data were acquired. We utilized traditional tools of center of pressure analysis, such as range, median frequency and frequency dispersion, as well as non-linear tools such as Sample Entropy for both the medial-lateral and anterior-posterior directions. At 12 months we used the Mullen Scales of Early Learning, the Communication and Symbolic Behavior Scales Developmental Profile™ and the Ages and Stages Questionnaire, the personal-social subscale. FINDINGS: At 6 months none of the postural control measures showed statistically significant differences between groups. Infants at high-risk presented significantly lower scores in all behavioral domains than infants at low-risk at 12 months with fair effect sizes. Certain measures of postural control at 6 months could predict language and visual reception behavior at 12 months. INTERPRETATION: Infants at high-risk for autism spectrum disorder present with delays in social, communication and language behavior as well as altered postural control in the first year of life. The present data support the possibility that motor skills and specifically postural control may drive the development in other domains.

Hip position influences shear wave elastography measurements of the hamstring muscles in healthy subjects.

Ultrasound shear wave elastography (SWE) has recently emerged as a non-invasive tool for assessing muscle stiffness. The majority of studies utilizing SWE have focused primarily on upper-extremity muscles, with little attention attributed to lower-extremity muscles. In addition, of the studies that have been published, various joint and muscle positions have been examined, rendering it difficult to compare results across studies. Thus, the purpose of this investigation was to examine lower extremity medial hamstring muscles (semitendinosus and semimembranosus) and to determine how hip position (0° versus 90°) and muscle position (knee flexed versus extended) impacted resulting shear modulus values. Ten subjects varying widely in age participated in this study, and their hamstring stiffness was assessed in four separate positions: seated with the knee flexed and extended, and lying prone with the knee flexed and extended. Higher shear modulus values were found at the group-level when participants were seated compared to prone (hip placed at 90° compared to 0°). In addition, higher values were also found when the knee was extended compared to flexed, but only when the hip was placed at 90° (not 0°). These results demonstrate that joint and muscle position, particularly when assessing the hamstrings, largely impact resulting shear modulus values. Therefore, joint and muscle position need to be systematically controlled for and reported when establishing normative ranges for shear modulus values across specific age groups. This will enable physicians to more precisely determine whether patients' shear modulus values indicate clinically meaningful differences in comparison to normative data.

The Likelihood of Self-reporting Balance Problems in Those With Advanced Chronic Kidney Disease, Slow Gait Speed, or Low Vitamin D.

OBJECTIVE: The purpose of this study was to determine the prevalence of vitamin D (25(OH)D) and balance deficits in persons with chronic kidney disease (CKD) and the likelihood of self-reporting balance and falling problems, measured gait speed in persons with kidney disease, and low levels of vitamin D and albumin. DESIGN: Analysis of the National Health and Nutrition Examination Survey 1999-2004 data set. SUBJECTS: The study included 8,554 subjects aged >40 years who were categorized into CKD stages based on the glomerular filtration rate (normal kidney function and stages 1 and 2 served as the control group, and stages 3 and 4/5 served as the CKD groups). MAIN OUTCOME MEASURES: Measured 25(OH)D levels, timed 20-feet walk, Romberg standing balance task, and self-reported balance and falling issues. RESULTS: The prevalence of balance deficits was found to be high in this CKD sample, with fail rates increasing with kidney disease severity. Similarly, when examining the relationship between CKD stage and the measurement of balance, fail rates (impaired balance) increased and gait speed decreased with kidney disease severity. In addition, the likelihood of self-reporting a balance and falling problem in the past year was higher in persons who had advanced CKD, were of older age, were of female sex, were with former or current smoking status, had lower 25(OH)D levels, and had lower albumin levels. Similarly, the likelihood of having a 20-feet walk time of more than 8 seconds was associated with those who were older, had higher body mass index, and had lower levels of 25(OH)D and albumin. CONCLUSION: The unique finding of this study is that increased reporting of balance and falling issues (both perceived and measured) and slower gait were found in persons with increased CKD severity and lower 25(OH)D status.

Reliability of center of pressure measures for assessing the development of sitting postural control through the stages of sitting.

Cerebral palsy (CP) impairs an individual's ability to move and control one's posture. Unfortunately, the signs and symptoms of CP may not be apparent before age two. Evaluating sitting posture is a potential way to assess the developing mechanisms that contribute to CP. The purpose of this project was to determine the reliability of linear and nonlinear measures, including inter- and intrastage reliability, when used to analyze the center of pressure (COP) time series during the stages of sitting development in children with typical development (TD) and with/at-risk for cerebral palsy (CP). We hypothesized that nonlinear tools would be more reliable than linear tools in assessing childrens' sitting development, and reliability would increase with development. COP data was recorded for three trials at eight sessions. Linear parameters used were root mean square, range of sway for the anterior-posterior (AP) and medial-lateral (ML) directions, and sway path. Nonlinear parameters used were Approximate Entropy, the largest Lyapunov Exponent, and Correlation Dimension for the AP and ML direction. Participants consisted of 33 children with TD and 26 children with/at-risk for CP. Our results determined that COP is a moderately reliable method for assessing the development of sitting postural control in stages in both groups. Thus, clinicians may be able to use measures from COP data across stages to assess the efficacy of therapeutic interventions that are intended to improve sitting postural abilities in children with/at-risk for CP.

A Perceptual Motor Intervention Improves Play Behavior in Children with Moderate to Severe Cerebral Palsy.

For children with moderate or severe cerebral palsy (CP), a foundational early goal is independent sitting. Sitting offers additional opportunities for object exploration, play and social engagement. The achievement of sitting coincides with important milestones in other developmental areas, such as social engagement with others, understanding of spatial relationships, and the use of both hands to explore objects. These milestones are essential skills necessary for play behavior. However, little is known about how sitting and play behavior might be affected by a physical therapy intervention in children with moderate or severe CP. Therefore, our overall purpose in this study was to determine if sitting skill could be advanced in children with moderate to severe CP using a perceptual motor intervention, and if play skills would change significantly as sitting advanced. Thirty children between the ages of 18 months and 6 years who were able to hold prop sitting for at least 10 s were recruited for this study. Outcome measures were the sitting subsection of the Gross Motor Function Measure (GMFM), and the Play Assessment of Children with Motor Impairment play assessment scale, which is a modified version of the Play in Early Childhood Evaluation System. Significant improvements in GMFM sitting scores (p < 0.001) and marginally significant improvement in play assessment scores (p = 0.067) were found from pre- to post-intervention. Sitting change explained a significant portion of the variance in play change for children over the age of 3 years, who were more severely affected by CP. The results of this study indicate that advances in sitting skill may be a factor in supporting improvements in functional play, along with age and severity of physical impairment.