Modifying quantitative sensory testing to investigate behavioral reactivity in a pediatric global developmental delay sample: Relation to peripheral innervation and chronic pain outcomes.

Early tactile and nociceptive (pain) mechanisms in children with global developmental delay at risk for intellectual and developmental disability are not well understood. Sixteen children with global developmental delay (mean age = 5.1 years, SD = 1.4; 50% male) completed a modified quantitative sensory testing (mQST) protocol, an epidermal (skin) punch biopsy procedure, and parent-endorsed measures of pain. Children with reported chronic pain had significantly greater epidermal nerve fiber density (ENFd) compared to children without chronic pain. Based on the mQST trials, ENFd values were associated with increased vocal reactivity overall and specifically during the light touch and cool thermal stimulus trials. The findings support the feasibility of an integrative biobehavioral approach to test nociceptive and tactile peripheral innervation and behavioral reactivity during a standardized sensory test in a high-risk sample for which there is often sensory dysfunction and adaptive behavior impairments.

A systematic review of risk for the development and persistence of self-injurious behavior in intellectual and developmental disabilities.

Self-injurious behavior (SIB) by individuals with intellectual and developmental disabilities including autism (I/DD) is among the most clinically disturbing, socially costly, and scientifically challenging behavior disorders. Forty years of clinical research has produced a knowledge base supporting idiographic behavioral assessment and treatment approaches. Despite the treatment progress, from a public health and population perspective, we argue it is less clear that we have reduced the disorder's burden. The developmental course of the disorder is mostly unknown and empirically informed population-level models of risk are absent. In this review, we systematically examined the published scientific literature specific to risk for SIB in the I/DD population. We reviewed study methodology in detail intentionally informed by an epidemiological perspective with a set of questions intended to test the quality of the inferences about risk. Results are discussed in terms of conceptual, methodological, and translational issues with respect to what needs to be done to create credible and useful clinical models for SIB risk in the I/DD population.

Pain burden in children with cerebral palsy (CPPain) survey: Study protocol.

Pain is a significant health concern for children living with cerebral palsy (CP). There are no population-level or large-scale multi-national datasets using common measures characterizing pain experience and interference (ie, pain burden) and management practices for children with CP. The aim of the CPPain survey is to generate a comprehensive understanding of pain burden and current management of pain to change clinical practice in CP. The CPPain survey is a comprehensive cross-sectional study. Researchers plan to recruit approximately 1400 children with CP (primary participants) across several countries over 6-12 months using multimodal recruitment strategies. Data will be collected from parents or guardians of children with CP (0-17 years) and from children with CP (8-17 years) who are able to self-report. Siblings (12-17 years) will be invited to participate as controls. The CPPain survey consists of previously validated and study-specific questionnaires addressing demographic and diagnostic information, pain experience, pain management, pain interference, pain coping, activity and participation in everyday life, nutritional status, mental health, health-related quality of life, and the effect of the COVID-19 pandemic on pain and access to pain care. The survey will be distributed primarily online. Data will be analyzed using appropriate statistical methods for comparing groups. Stratification will be used to investigate subgroups, and analyses will be adjusted for appropriate sociodemographic variables. The Norwegian Regional Committee for Medical and Health Research Ethics and the Research Ethics Board at the University of Minnesota in USA have approved the study. Ethics approval in Canada, Sweden, and Finland is pending. In addition to dissemination through peer-reviewed journals and conferences, findings will be communicated through the CPPain Web site (www.sthf.no/cppain), Web sites directed toward users or clinicians, social media, special interest groups, stakeholder engagement activities, articles in user organization journals, and presentations in public media.

Presence and predictors of pain after orthopedic surgery and associated orthopedic outcomes in children with cerebral palsy.

While children with cerebral palsy (CP) may undergo 8-22 orthopedic surgeries in their lifetime, little is known about the associated pain. We aimed to assess the pain presence before and one year after lower extremity orthopedic surgery, predictors of pain presence at follow-up, and the association between pain and orthopedic outcomes related to surgery. This retrospective study included 86 children with CP (M age = 10.0 years, SD = 3.2; range = 4.1-17.3 years, Gross Motor Functional Classification System (GMFCS) level I-III) who underwent orthopedic surgery and had completed questionnaires at gait analyses before (M = 2.7 months; range = 0.0-5.7) and after surgery (M = 11.8 months; range = 9.0-14.9). Pain presence, location, and Pediatric Outcomes Data Collection Instrument (PODCI) scores were documented before and after surgery at gait analyses. Pain prevalence was 60% at baseline and 56% at follow-up. Significant predictors of pain presence at follow-up included (1) pain presence at baseline (range of odds ratios [OR] across any/all locations = 3.22 to 15.54), (2) older age (range of OR for any pain, back, knee, and foot pain = 1.24-1.26), (3) female sex (decreased OR for males for ankle pain = 0.12), (4) having hip surgery (decreased OR for foot pain = 0.20), and (5) lower GMFCS level (OR for foot pain = 0.41). Changes in PODCI Sports and Physical Function scores were associated with changes in hip and knee pain (P < .03); PODCI scores worsened for patients who had pain at both time points and improved for patients who had pain at baseline but not follow-up. Pain was present for over half of the participants before and after orthopedic surgery. Pain presence at follow-up was predicted by pain presence at baseline. Pain and functional outcomes were correlated at follow-up. Prospective studies examining perioperative pain experience and factors predicting pain outcomes are warranted.

[Challenges in pain assessment and management among individuals with intellectual and developmental disabilities : German version]. / Herausforderungen der Schmerzerfassung und -therapie bei Personen mit Intelligenzminderung und Entwicklungsstörungen : Deutsche Fassung.

INTRODUCTION: Intellectual and developmental disabilities (IDD) include conditions associated with physical, learning, language, behavioural, and/or intellectual impairment. Pain is a common and debilitating secondary condition compromising functional abilities and quality of life. OBJECTIVES: This article addresses scientific and clinical challenges in pain assessment and management in individuals with severe IDD. METHODS: This Clinical Update aligns with the 2019 IASP Global Year Against Pain in the Vulnerable and selectively reviews recurring issues as well as the best available evidence and practice. RESULTS: The past decade of pain research has involved the development of standardized assessment tools appropriate for individuals with severe IDD; however, there is little empirical evidence that pain is being better assessed or managed clinically. There is limited evidence available to inform effective pain management practices; therefore, treatment approaches are largely empiric and highly variable. This is problematic because individuals with IDD are at risk of developing drug-related side effects, and treatment approaches effective for other populations may exacerbate pain in IDD populations. Scientifically, we are especially challenged by biases in self-reported and proxy-reported pain scores, identifying valid outcome measures for treatment trials, being able to adequately power studies due to small sample sizes, and our inability to easily explore the underlying pain mechanisms due to compromised ability to self-report. CONCLUSION: Despite the critical challenges, new developments in research and knowledge translation activities in pain and IDD continue to emerge, and there are ongoing international collaborations.

Expression of and correlational patterns among neuroinflammatory, neuropeptide, and neuroendocrine molecules from cerebrospinal fluid in cerebral palsy.

BACKGROUND: The underlying pathogenesis of cerebral palsy (CP) remains poorly understood. The possibility of an early inflammatory response after acute insult is of increasing interest. Patterns of inflammatory and related biomarkers are emerging as potential early diagnostic markers for understanding the etiologic diversity of CP. Their presence has been investigated in plasma and umbilical cord blood but not in cerebrospinal fluid (CSF). METHODS: A clinical CP sample was recruited using a single-time point cross-sectional design to collect CSF at point-of-care during a standard-of-care surgical procedure (intrathecal pump implant). Patient demographic and clinical characteristics were sourced from medical chart audit. RESULTS: Significant (p ≤ 0.001) associations were found among neuroinflammatory, neuroendocrine, and nociceptive analytes with association patterns varying by birth status (term, preterm, extremely preterm). When between birth-group correlations were compared directly, there was a significant difference between preterm and extremely preterm birth subgroups for the correlation between tumour necrosis factor alpha (TNFα) and substance P. CONCLUSION: This investigation shows that CSF can be used to study proteins in CP patients. Differences in inter-correlational patterns among analytes varying by birth status underscores the importance of considering birth status in relation to possible mechanistic differences as indicated by biomarker signatures. Future work should be oriented toward prognostic and predictive validity to continue to parse the heterogeneity of CP's presentation, pathophysiology, and response to treatment.

Caregiver-Reported Pain Management Practices for Individuals With Cerebral Palsy.

OBJECTIVE: To investigate types and intensity of pain experienced by individuals with cerebral palsy (CP) and common pain-relieving approaches used by caregivers. DESIGN: The approach was cross-sectional, using standardized interviews. SETTING: Individuals with CP were recruited from a specialty health care hospital. PARTICIPANTS: Eighty-six individuals (N=86; mean age, 17.2 years; male, 58%) with CP and complex communication needs participated. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Pain type, mean pain intensity (MPI) (graded on a scale of 0=no pain to 10=worst possible pain), and mean pain relief (MPR) (graded on a scale of 0=intervention did not help at all to 10=intervention completely relieved pain) were assessed by caregiver report as part of the Dalhousie Pain Interview for each type of pain experienced in the previous 7 days. RESULTS: Caregivers reported that 58 participants (67%) had experienced pain in the previous 7 days. MPI was 7.7±1.8 when the pain was worst in the previous 7 days. The 2 most common types of pain included musculoskeletal pain (n=70) and gastrointestinal pain (n=11). The most frequent treatment to relieve musculoskeletal pain was changing positions (n=27, MPI=5.1±2.3, MPR=6.6±2.1), medication (n=25, MPI=7.4±1.6, MPR=5.3±1.9), and massage (n=19, MPI=6.7±1.9, MPR=5.2±1.7). To treat gastrointestinal pain, medication was typically used (n=4, MPI=4.8±1.4, MPR=5.5±1.0), although no treatment was just as common (n=4, MPI=4.5±2.3). CONCLUSIONS: The results indicate that musculoskeletal pain is prevalent in individuals with CP, and changing physical positions and providing medication are strategies most used by caregivers.

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.

Delay to Early Intensive Behavioral Intervention and Educational Outcomes for a Medicaid-Enrolled Cohort of Children with Autism.

Increased prevalence of autism spectrum disorder (ASD) has underscored the need for early intervention services. Early Intensive Behavioral Intervention (EIBI) is among the most common evidence-based approaches, however, stakeholders report significant waitlists. The effects of these delays to intervention are unknown. The purpose of this study was to evaluate the effects of delay to EIBI for preschool aged children with ASD on later educational outcomes. Medicaid records from Minnesota (2008-2010) were used to evaluate a cohort diagnosed with ASD and their later educational outcomes from 2010 to 2014 (n = 667) using generalized estimating equations. Approximately 70% of children experienced a delay to EIBI and children that experienced less delay and started EIBI at a younger age had better educational outcomes.

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.

Challenges in pain assessment and management among individuals with intellectual and developmental disabilities.

INTRODUCTION: Intellectual and developmental disabilities (IDD) include conditions associated with physical, learning, language, behavioural, and/or intellectual impairment. Pain is a common and debilitating secondary condition compromising functional abilities and quality of life. OBJECTIVES: This article addresses scientific and clinical challenges in pain assessment and management in individuals with severe IDD. METHODS: This Clinical Update aligns with the 2019 IASP Global Year Against Pain in the Vulnerable and selectively reviews recurring issues as well as the best available evidence and practice. RESULTS: The past decade of pain research has involved the development of standardized assessment tools appropriate for individuals with severe IDD; however, there is little empirical evidence that pain is being better assessed or managed clinically. There is limited evidence available to inform effective pain management practices; therefore, treatment approaches are largely empiric and highly variable. This is problematic because individuals with IDD are at risk of developing drug-related side effects, and treatment approaches effective for other populations may exacerbate pain in IDD populations. Scientifically, we are especially challenged by biases in self-reported and proxy-reported pain scores, identifying valid outcome measures for treatment trials, being able to adequately power studies due to small sample sizes, and our inability to easily explore the underlying pain mechanisms due to compromised ability to self-report. CONCLUSION: Despite the critical challenges, new developments in research and knowledge translation activities in pain and IDD continue to emerge, and there are ongoing international collaborations.

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.

Musculoskeletal Pain Outcomes Pre- and Post Intrathecal Baclofen Pump Implant in Children With Cerebral Palsy: A Prospective Cohort Study.

OBJECTIVE: To characterize musculoskeletal pain intensity, duration, frequency, and interference with activities of daily living in children with cerebral palsy (CP) before and after intrathecal baclofen pump placement. DESIGN: Prospective cohort study. SETTING: Children's tertiary hospital. PARTICIPANTS: Participants were children with CP (N=32; 53% male; mean age, 9.9y; age range, 4-17y). The majority of participants had a CP diagnosis of quadriplegia (76%) and relied on wheeled mobility (91%). INTERVENTIONS: Assessments were completed pre- and post intrathecal baclofen pump implant. MAIN OUTCOME MEASURES: Because of considerable patient heterogeneity, both pain measures (Brief Pain Inventory, Dalhousie Pain Interview) were completed by proxy (parent) report at the time of the procedure and approximately 6 months after intrathecal baclofen (ITB) pump placement. RESULTS: Prior to implant, 31% of participants were living with constant pain, which reduced to 6% post ITB implant (P<.001). Based on Wilcoxon signed rank tests, pain duration significantly decreased post ITB pump implant (P<.01). CONCLUSIONS: This prospective analysis supports the anecdotal and retrospective evidence that musculoskeletal pain decreases in CP following ITB pump implant. The greatest effect appears to be on the duration of pain experience. Pain did not decrease for all individuals, and it would be worth further investigation to better understand the relation between patient characteristics and pain outcomes.

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.

Investigating the Feasibility of a Modified Quantitative Sensory Testing Approach to Profile Sensory Function and Predict Pain Outcomes Following Intrathecal Baclofen Implant Surgery in Cerebral Palsy.

OBJECTIVES: Intrathecal baclofen (ITB) pumps used to manage spasticity in children with cerebral palsy (CP) also improve pain outcomes for some but not all patients. The purpose of this clinical feasibility study was to explore whether a quantitative sensory testing approach could a) be modified and used to subgroup individuals into sensory profiles and b) test whether the profiles were related to postimplant pain outcomes (i.e., pain responsive or pain persistent). SUBJECTS: A purposeful clinical sample of nine children with CP (mean age = 12.5 years, male = 56%) and complex communication needs participated. METHODS: A prospective within-subject design was used to measure proxy-reported pain before and after ITB implant. Pain response status was determined by proxy-reported pain intensity change (>50% change in maximum rated intensity). A modified quantitative sensory testing (mQST) procedure was used to assess behavioral responsivity to an array of calibrated sensory (tactile/acute nociceptive) stimuli before surgery. RESULTS: Seven individuals with presurgical pain had mQST differentiated sensory profiles in relation to ITB pain outcomes and relative to the two individuals with no pain. Presurgically, the ITB pain responsive subgroup (N = 3, maximum rated pain intensity decreased >50% after ITB implant) showed increased behavioral reactivity to an acute nociceptive stimulus and cold stimulus, whereas the ITB pain persistent subgroup (N = 4) showed reduced behavioral reactivity to cold and repeated von Frey stimulation relative to the no pain individuals. CONCLUSION: Implications for patient selection criteria and stratification to presurgically identify individuals with CP "at risk" for persistent postprocedure pain are discussed.

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.