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

Abstract

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.

Wild-type MECP2 expression coincides with age-dependent sensory phenotypes in a female mouse model for Rett syndrome

“…Disruption of primary sensory processing is evident in X-linked neurodevelopmental disorders such as Autism Spectrum Disorder and Rett syndrome (Buchanan et al, 2019; Djukic et al, 2012; Djukic & Valicenti McDermott, 2012; Key et al, 2019; LeBlanc et al, 2015; Merbler et al, 2020; Nomura, 2005; Peters et al, 2015; Symons et al, 2019). Such disruptions during development and adulthood likely contributes to motor dysfunction and social communication deficits in girls and women with Rett syndrome.…”

“…Diagnostic criteria for RTT include partial or complete loss of acquired purposeful motor skills or spoken language during a regression period in the first few years of life. Additionally, primary sensory processing is disrupted in RTT patients (Buchanan et al, 2019; Djukic et al, 2012; Djukic and Valicenti McDermott, 2012; Key et al, 2019; LeBlanc et al, 2015; Merbler et al, 2020; Nomura, 2005; Peters et al, 2015; Stallworth et al, 2019; Symons et al, 2019). Such disruptions during development and adulthood contribute to motor dysfunction and social communication deficits in girls and women with RTT.…”

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

“…Such an approach sacrifices the ability to measure cutaneous sensory thresholds of various modalities. We have initiated such an approach in multiple clinical and field-based settings with multiple populations that have developmental disabilities and neurodegenerative diseases with evidence of excellent validity and very good psychometric properties in different applications, but we, heretofore, have not used it as a tool to integrate behavioral outcome measures with biomarkers specific to peripheral innervation (Barney et al, 2015(Barney et al, , 2017(Barney et al, , 2020Merbler et al, 2020;Symons et al, 2010).…”

Movement disorders in patients with Rett syndrome: A systematic review of evidence and associated clinical considerations

“…Visual cues of EBAD symptoms such as pain may also be blunted by impaired movements 79 and because previous reports have suggested that parents were unsure of whether their child had experienced pain in the last month, 80 it reinforces the notion that proactive monitoring of EBAD symptoms to reduce sensory stressors are critical in RTT. Baseline heart rate variability 81 and using electrodermal activity to monitor the impact of stressors on chronic illness in patients with RTT 82 could be options to assist clinicians in the management of EBAD and its impact on movement disorders in this patient group.…”