Self and caregiver report measurement of sensory features in autism spectrum disorder: a systematic review of psychometric properties.

BACKGROUND: Unusual responses to sensory stimuli are considered a diagnostic symptom of autism spectrum disorder with mounting research efforts put towards understanding, characterizing, and treating such symptoms. METHODS: This paper examines self and caregiver report tools used to measure sensory features in ASD through a systematic review of the psychometric evidence for their use. A total of 31 empirical papers were reviewed across 20 assessment tools. Substantial differences were identified in the specific sensory features defined across assessment tools. Sensory assessment questionnaires were evaluated against quality psychometric evidence criteria to provide a use recommendation. RESULTS: Five assessments were identified to be "appropriate with conditions," while no sensory assessment tools were identified to have sufficient quality psychometric evidence to provide a recommendation of "Appropriate" for measuring sensory features in ASD. CONCLUSION: Evidence from this review highlights potentially significant shortcomings among the current methods used to measure sensory features in ASD and suggests the need for more efforts in developing psychometrically sound sensory assessment tools for use in ASD populations.

Parental Pain Catastrophizing, Communication Ability, and Post-surgical Pain Outcomes Following Intrathecal Baclofen Implant Surgery for Patients With Cerebral Palsy.

There is strong evidence that psychosocial variables, including pain catastrophizing, influence parental and child ratings of pain, pain expression, and long-term outcomes among children with chronic pain. The role of these factors among children who have communication deficits due to cerebral palsy (CP) and other intellectual and developmental disabilities is currently unclear. In this study, parental pain catastrophizing was assessed before intrathecal baclofen (ITB) pump implantation for spasticity management in 40 children and adolescents with CP, aged 4 to 24 years. Pain was assessed before and after surgery with two methods: a parent-reported pain interference scale, and behavioral pain signs during a standardized range of motion exam. Linear mixed models with clinical/demographic factors and scores from the Pain Catastrophizing Scale for Parents (PCS-P), and child spoken language ability as predictors and the pain variables as the outcomes were implemented. On average, both pain outcomes improved after surgery. Only child spoken language ability predicted change in behavioral reactivity scores, with children with phrase speech showing an increase in reactivity at follow-up compared to pre-surgery levels, on average. A significant interaction between PCS-P scores and spoken language ability on change in pain interference scores over time showed that dyads with children with phrase speech whose parents reported high PCS-P scores reported the least improvement in pain interference at follow-up. Due to the preliminary nature of the study, future work is needed to investigate the parental behaviors that mediate the relationships between parental catastrophizing and pain outcomes in this population.

Associations Among Diurnal Salivary Cortisol Patterns, Medication Use, and Behavioral Phenotype Features in a Community Sample of Rett Syndrome.

Rett syndrome (RTT) is a severe neurodevelopmental disorder resulting from mutations of the MECP2 gene. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and abnormal stress responses have been observed in animal models of RTT, but little is known about HPA axis function among individuals with RTT. Diurnal salivary cortisol patterns from 30 females with RTT were examined in relation to mutation type, medication use, and features of the RTT behavioral phenotype. Cortisol patterns were significantly related to mutation severity, anticonvulsant medication status, and bruxism (tooth grinding). This study provides preliminary support for the hypothesis that RTT may be at risk for outcomes associated with aberrant HPA axis function, and that this risk may be mediated by mutation type.

Special Education Supports and Services for Rett Syndrome: Parent Perceptions and Satisfaction.

There are no published studies describing educational experiences for girls with Rett syndrome. Given the extensive educational needs associated with Rett syndrome, it is important to understand how families perceive their daughters' educational experiences to inform education service provision. The purpose of this study was to survey parents of school-aged children with Rett syndrome to describe the educational services that they receive and understand parents' perceptions of and satisfaction with the special educational and related services. The majority of parents were satisfied with their daughters' educational services. Communication was the most frequently endorsed priority skill area, and many parents expressed frustration with limited access to augmentative and alternative communication (AAC) devices and staff training in their use. These results suggest there is a need for high-quality speech therapy and an emphasis on AAC support.

Preliminary Evidence That Resting State Heart Rate Variability Predicts Reactivity to Tactile Stimuli in Rett Syndrome.

Patients with Rett syndrome may manifest altered pain perception/experience and are vulnerable to conditions associated with chronic pain. Pain response is difficult to measure, however, because of severe communicative impairment. There is also documented autonomic dysfunction, including decreased heart rate variability. Given the relation between pain and the autonomic nervous system, we tested the feasibility of using resting heart rate variability to predict nonverbal pain/discomfort behavior during a standardized modified quantitative sensory test in Rett syndrome. All stimulus applications resulted in increased behavioral reactivity compared to baseline, with repeated von Frey significantly greater than all other stimuli. Resting heart rate variability predicted behavioral reactivity to repeated von Frey. These preliminary findings provide feasibility evidence for an integrated autonomic-sensory measurement approach and are consistent at a construct level with preclinical evidence in Rett syndrome. Further work is needed to determine how heart rate variability changes during stimulus application.

An exploration of the interrater agreement of visual analysis with and without context.

Visual analysis is integral to the analysis of single-case experimental design (SCED) data. Previous studies have shown that many factors may influence the interrater agreement (IRA) of visual analysis. One factor that has received little direct attention is the impact of contextual information. In the current study, authors of recently published SCED studies were asked to make judgments regarding functional relations based on published datasets that met criteria for design quality. Respondents were randomly assigned to view graphs with or without contextual information and the degree of interrater agreement was compared. Results revealed that contextual information had no impact on IRA for decisions of a functional relation. IRA was high across both groups for 6 of the 7 datasets examined. Implications and recommendations based on these results are discussed.

Evidence of altered salivary cytokine concentrations in Rett syndrome and associations with clinical severity.

Background: Immune dysregulation may play a role in the development of Rett syndrome (RTT), a neurodevelopmental disorder caused by mutations of the MECP2 gene. Abnormal cytokine concentrations have been documented in the serum of individuals with RTT. Measurement of salivary cytokines has been investigated as a potential alternative approach to measurement in blood and serum, but it is unclear whether salivary cytokine concentrations can provide valid information about systemic immune function in neurodevelopmental disorders. The goal of this study was to evaluate the potential validity of salivary cytokines as biomarkers of immune dysregulation in RTT. Methods: Saliva samples from 16 individuals with RTT (all female; age range 2-40 years) and 16 healthy control females (age range 2-40 years) were analyzed for concentrations of 12 cytokines. Between-group differences in concentrations, and correlations with clinical severity in the RTT group were evaluated. Results: Concentrations of several salivary cytokines (IL-1ß, IL-6, IL-8, IL-10, GM-CSF, TNF-α, and VEGF) were increased in RTT compared to controls. The same cytokines showed significant positive correlations with clinical severity scores. There were no differences in concentrations of IL-2, IL-4, IL-5, IL-12p70, and IFN-γ. Conclusion: The results suggest that salivary cytokines may be a possible indicator of immune dysregulation in RTT. Future research should investigate whether these results can be applied to other neurodevelopmental disorders.

A clinical case-control comparison of epidermal innervation density in Rett syndrome.

INTRODUCTION: Rett syndrome (RTT), a rare neurodevelopmental disorder occurring primarily in females (1:10-15,000 female live births), is most often caused by loss-of-function mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2). Clinical observations and preclinical findings indicate apparent abnormal sensory and nociceptive function. There have been no direct investigations of epidermal sensory innervation in patients with RTT. METHODS: We compared 3 mm epidermal punch biopsy specimens from adolescent female RTT patients (N = 4, aged 12-19 years) against an archived approximate age-, sex-, body-site matched comparison sample of healthy adolescent females (N = 8, ages 11-17). RESULTS: Confocal imaging revealed, on average, statistically significant increased epidermal nerve fiber (ENF) peptidergic (co-stained calcitonin gene-related protein [CGRP]) innervation density compared with healthy female control individuals. CONCLUSIONS: Given the clinical phenotype of disrupted sensory function along with diagnostic criteria specific to cold hands/feet and insensitivity to pain, our preliminary observations of ENF peptidergic fiber density differences warrants further investigation of the peripheral neurobiology in RTT.

Promoting Conditional Use of Communication Skills for Learners With Complex Communication Needs: A Tutorial.

Purpose: Conditional use of communication skills refers to the ability of a learner to appropriately generalize and discriminate when, where, and how to communicate based on constant variation and shifts in environmental cues. Method: We describe discrimination and generalization challenges encountered by learners with complex communication needs and ways in which these challenges are fostered through traditional communication intervention programming. We address arrangements in instruction that maximize the probability of learners acquiring the conditional use of new vocabulary and the modest instructional technology implemented when planning for generalization. Results: We propose establishing well-discriminated and generalized use of new vocabulary items through the application of a general case instruction framework to communication intervention programming. Conclusion: We provide intervention methodology, including intervention steps for general case instruction, a plethora of functional examples, and graphic displays to assess and intervene to promote conditional use of communication skills for learners with complex communication needs.

The feasibility of using actigraphy to characterize sleep in Rett syndrome.

BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder primarily caused by mutations in the MECP2 gene. Sleep problems are reported by the majority of caregivers of individuals with RTT. METHODS: The present study aimed to replicate and extend previous work about the feasibility of measuring sleep with an actigraph device in a sample of girls with clinically diagnosed RTT (N = 13, mean age = 9 years, 5 months). Participants wore an actigraph device day and night for seven consecutive days. Materials also included a parent-completed sleep diary to measure bedtime, duration of nighttime sleep, and daytime sleep, and the Child Sleep Habit's Questionnaire (CSHQ). RESULTS: The means for the sample as measured by actigraphy were 492.3 min (SD = 47.3) of total night sleep (TNS), 76.0% (SD = 6.7) sleep efficiency, 86.0 min (SD = 34.2) of wake after sleep onset, and 46.1 min (50.8) of sleep when parents reported a nap occurring. Parents reported 589.7 min (SD = 53.6) of TNS, 15.9 min (SD = 12.0) of WASO, and 93.6 min (SD = 66.8) of daytime sleep according to sleep diaries, with all parents reporting at least one nap during the week. Relations were found between sleep characteristics and seizure status and CSHQ total scores. No age-related changes were observed for any sleep characteristic, regardless of collection method. Five of nine participants above the cutoff score on the CSHQ indicate the need for further evaluation for a sleep disorder. CONCLUSIONS: Overall, actigraphy was feasible in this community-based sample of girls with RTT. The results replicated some aspects of previous studies of sleep in RTT (e.g., no age-related changes in total nighttime sleep or efficiency). Some participants met the American Academy of Sleep Medicine guidelines for recommended total sleep time, with others showing too much or too little sleep. Each of the three methods for describing sleep presented its own advantages and challenges. Future work should be prospectively designed, validate the use of actigraphy in this population, and include a typically developing comparison sample to improve the precision of our understanding of sleep in RTT.

A case-controlled comparison of postoperative analgesic dosing between girls with Rett syndrome and girls with and without developmental disability undergoing spinal fusion surgery.

BACKGROUND: Rett syndrome is associated with severe motor and communicative impairment making optimal postoperative pain management a challenge. There are case reports documenting reduced postoperative analgesic requirement in Rett syndrome. AIM: The goal of this preliminary investigation was to compare postoperative analgesic management among a sample of girls with Rett syndrome compared to girls with and without developmental disability undergoing spinal fusion surgery. METHOD: The medical records of eight girls with Rett syndrome (mean age = 13.2 years, sd = 1.9), eight girls with developmental disability (cerebral palsy; mean age = 13.1 years, sd = 2.0), and eight girls without developmental disability (adolescent idiopathic scoliosis; mean age = 13.4, sd = 1.8) were reviewed. Data related to demographics, medications, and route of drug administration were recorded. RESULTS: Girls with Rett syndrome received significantly fewer morphine equivalent opioids postoperatively (M = 0.26 mg·kg-1 ·day-1 , sd = 0.10) compared to girls with adolescent idiopathic scoliosis (M = 0.47mg·kg-1 ·day-1 , sd = 0.13; 95% CI -0.34 to -0.08; P = 0.001) and girls with CP (M = 0.40 mg·kg-1 per day, sd = 0.14; 95% CI -0.27 to -0.02; P = 0.01). Girls with Rett syndrome received significantly fewer opioid patient-controlled analgesic (PCA) bolus doses (given by proxy; M = 42.63, sd = 17.84) compared to girls with adolescent idiopathic scoliosis (M = 98.25, sd = 52.77; 95% CI -96.42 to -14.83; P = 0.01). There was also some evidence indicating girls with Rett syndrome received fewer bolus doses compared to girls with CP (M = 80.88, sd = 38.93; 95% CI -79.05 to 2.55; P = 0.06). On average, girls with Rett syndrome also received smaller total doses of acetaminophen, diazepam, and hydroxyzine. CONCLUSION: This study highlights possible discrepancies in postoperative pain management specific to girls with Rett syndrome and suggests further investigation is warranted to determine best practice for postoperative analgesic management for this vulnerable patient population.

Diurnal Salivary Cortisol and Regression Status in MECP2 Duplication Syndrome.

MECP2 duplication syndrome is an X-linked genomic disorder that is characterized by infantile hypotonia, intellectual disability, and recurrent respiratory infections. Regression affects a subset of individuals, and the etiology of regression has yet to be examined. In this study, alterations in the hypothalamus-pituitary-adrenal axis, including diurnal patterns in salivary cortisol, were examined in 4 males with MECP2 duplication syndrome who had regression and 4 males with the same syndrome without regression (aged 3-22 years). Individuals who had experienced regression do not exhibit typical diurnal cortisol rhythms, and their profiles were flatter through the day. In contrast, individuals with MECP2 duplication syndrome who had not experienced regression showed more typical patterns of higher cortisol levels in the morning with linear decreases throughout the day. This study is the first to suggest a link between atypical diurnal cortisol rhythms and regression status in MECP2 duplication syndrome and may have implications for treatment.

Infrared Thermal Analysis and Individual Differences in Skin Temperature Asymmetry in Rett Syndrome.

PURPOSE: We evaluated the feasibility of using a portable infrared thermal camera to quantify the degree of thermal dysregulation (cold hands/feet) and test for naturally occurring within-patient skin temperature asymmetry in Rett syndrome. PROCEDURES: Infrared thermal images were acquired passively from 15 patients (mean age = 13.7 years, range 4-47) with clinical diagnoses of Rett. Images were acquired using a FLIR T400 infrared thermal camera (still images recorded at 5 Hz, resolution of 320 × 240 pixels, thermal sensitivity = 0.05 °C; capture session lasted approximately 3 minutes). The infrared thermal camera was orthogonal to the body part (hands, feet) and positioned approximately 1 meter from the skin's surface. RESULTS: There were large intraindividual left/right differences in temperature. Seven (47%) and eight (53%) patients had statistically significant (P <0.05) left/right asymmetries between hands (mean difference = 0.87 °C, standard deviation = 1.21) and feet (mean difference = 1.73 °C, standard deviation = 3.03), respectively. Coders were reliable (intraclass correlations 0.97-0.99) on temperatures and selection of anatomical regions of interest. CONCLUSIONS: The degree of thermal asymmetry may reflect prolonged activity of the sympathetic nervous system and individual differences in sympathetic regulation. As clinical trials emerge and endpoints are considered, portable infrared thermal camera may provide one noninvasive means of evaluating changes in sympathetic regulation.

A Case-controlled Investigation of Pain Experience and Sensory Function in Neuronal Ceroid Lipofuscinosis.

OBJECTIVES: This case-control study explored pain experience and expression among individuals with neuronal ceroid lipofuscinosis (NCL) through parental report, tactile sensory testing, and infrared thermography (IRT). MATERIALS AND METHODS: Participants with NCL (n=8; M=14.8 y) and their unaffected siblings (n=8; M=23.5 y) were characterized in terms of pain response to a brief tactile sensory test (light touch, Von Frey monofilament). During sensory testing, behavioral expression was measured using the Battens Observational Pain Scale and infrared thermography (IRT) was used to quantify changes in skin/eye temperature. RESULTS: Children with NCL experienced pain frequently and from multiple sources that negatively impacted their lives. Children with NCL were reactive to the sensory testing as indexed by significant increased IRT temperature change (P<0.001). Across combined sensory conditions, individuals with NCL were significantly more reactive (Battens Observational Pain Scale total score) to sensory testing compared with siblings (P<0.05). Similarly, IRT difference scores between sensory conditions revealed a significant increase in temperature for individuals with NCL compared with siblings (P<0.001). DISCUSSION: Ongoing reported pain was a problem for the children with NCL in this sample. Increased pain expression during the repeated Von Frey filament suggests that the pathophysiology of the ongoing pain may be centrally mediated.

Functional communication training in rett syndrome: a preliminary study.

Rett syndrome (RTT) is associated with a range of serious neurodevelopmental consequences including severe communicative impairments. Currently, no evidence-based communication interventions exist for the population ( Sigafoos et al., 2009 ). The purpose of the current study was to examine the effectiveness of functional assessment (FA) and functional communication training (FCT) methods for teaching 3 individuals (ages 15-47 years) with classic RTT novel communicative behaviors. Using single-case experimental designs, functional reinforcers were identified (FA) and each participant quickly learned to activate a voice-output switch to obtain a reinforcer (FCT). These results suggest that individuals with classic RTT can learn novel communicative responses, which has important implications for future intervention research.

Rett syndrome: a preliminary analysis of stereotypy, stress, and negative affect.

Rett syndrome (RTT) is a neurodevelopmental disorder primarily affecting females. It is characterized by apparently normative development of motor and communicative abilities followed by deterioration in these domains. Stereotypic hand movements are one of the core diagnostic criteria for RTT. There is some anecdotal but limited scientific evidence that changes in hand stereotypy may be a sign of increased anxiety or arousal (i.e., a 'stress response') in RTT. Understanding stress responsivity is difficult in RTT because almost all individuals are nonverbal or otherwise severely communicatively impaired. This study used direct behavioral observation to quantify and compare the frequency of hand stereotypy and signs of negative affect during presumed periods of high and low stress associated with functional analysis conditions (negative reinforcement ['escape'] and control ['free play'], respectively) for 5 females with RTT (mean age=17.8; range 4-47). Negative affect was more likely to occur during negative reinforcement ('stress') conditions for each participant whereas hand stereotypies did not differ across conditions for any of the participants. Although preliminary, the results suggest that hand stereotypy may not be a valid behavioral 'stress-response' indicator in females with RTT. Alternatively, the approach we used may have been limited and not sufficient to evoke a stress response. Either way, more work with direct relevance to improving our understanding of hand stereotypy and anxiety in RTT in relation to social context appears warranted.

Seizures and pain uncertainty associated with parenting stress and Rett syndrome.

Data were collected parenting stress, adaptive behavior, pain, and health issues from the caregivers of 35 girls and women with Rett syndrome (mean age = 20.3). A majority (60%) of parents reported stress in the clinical range on at least 1 subscale of the Parenting Stress Index-Short Form. Seizures and uncertainty about their daughter's gastrointestinal pain experience were significantly associated with higher levels of parenting stress. No other child factors (adaptive behavior, age, residential status) were significantly related to parenting stress. Factors related to chronic health concerns (seizures, ambiguous pain presentation) may be important when considering family stress issues in relation to general outcomes for girls with Rett syndrome and related developmental disorders.

Effects of Positive and Negative Reinforcement in a Concurrent Operants Arrangement on Compliance and Problem Behavior / Efectos del Reforzamiento Positivo y Negativo en un Arreglo de Operantes Concurrentes sobre la Obediencia y la Conducta Problemática

Functional analysis (Iwata, Dorsey, Slifer, Bauman, & Richman, 1982/1994) is a robust approach to identifying function-based interventions for problem behavior, including self-injury, aggression, and destruction. Such interventions, however, may be difficult for untrained caregivers to implement with fidelity in natural environments. Further research is needed to identify simple antecedent strategies for promoting appropriate behavior among children with significant problem behavior. The purpose of the current study was to utilize a concurrent schedules arrangement to identify conditions under which two children with autism spectrum disorder (ASD) and developmental delays who engaged in problem behaviors would choose to complete academic tasks to earn access to preferred items. In both cases, problem behaviors were shown to be sensitive to reinforcement in the forms of escape from task demands and access to preferred items. A concurrent operant arrangement in which the participants could choose to complete work tasks to earn access to preferred activities, or to take a break without demands or preferred items, was implemented. The schedule requirements in the demand component were systematically increased across opportunities, while the amount and type of reinforcement was kept constant. The results show, at the lowest levels of task demands, both participants allocated more opportunities to the work option. At higher levels, however, both participants allocated a majority of their choices to the break option. Despite the absence of preferred items in the break component, no instances of problem behavior were observed following selection of the break option. This indicates that this type of analysis could be used to identify conditions for compliance among individuals who engage in escape- or multiply-maintained problem behaviors, without the need to provoke or reinforce problem behavior. Limitations of the current study and recommendations for future research are discussed.

El análisis funcional (Iwata, Dorsey, Slifer, Bauman, & Richman, 1982/1994) es una aproximación robusta para identificar intervenciones basadas en la función para la conducta problemática, incluyendo la autolesión, agresión y destrucción. Tales intervenciones, no obstante, pueden ser difíciles de implementar fidedignamente en escenarios naturales por cuidadores no entrenados. Se requiere más investigación para identificar estrategias antecedentes simples para promover la conducta apropiada entre niños con problemas significativos de conducta. El propósito del presente estudio fue utilizar un arreglo de programas concurrentes para identificar las condiciones bajo las cuales dos niños con trastorno del espectro autista (ASD, por sus siglas en inglés) y retraso en el desarrollo que emitían conducta problemática escogerían completar tareas académicas para ganar acceso a ítems preferidos. En ambos casos, las conductas problemáticas fueron sensibles al reforzamiento consistente en escape de las demandas de la tarea y en acceso a ítems preferidos. Se implementó un arreglo de programas concurrentes en el que los participantes podían escoger entre completar una tarea académica para ganar acceso a ítems preferidos o tomar un descanso sin demandas y sin ítems preferidos. Los requisitos del programa en el componente de demanda fueron incrementados sistemáticamente a través de las oportunidades de elección, mientras que el tipo y cantidad de reforzamiento se mantuvo constante. Los resultados mostraron que en el nivel más bajo de demandas, ambos participantes prefirieron la opción de trabajo. A niveles de demanda más altos, no obstante, ambos participantes eligieron la opción de tomar un descanso. A pesar de la ausencia de ítems preferidos en el componente de descanso, no se observaron instancias de conducta problemática después de esta opción. Esto indicó que este tipo de análisis puede ser usado para identificar condiciones que conducen a la obediencia entre individuos cuya conducta problemática se mantiene por escape o bien por múltiples reforzadores, sin la necesidad de provocar o reforzar la conducta problemática. Se discuten las limitaciones del presente estudio y se ofrecen recomendaciones para futura investigación.