Autonomic dysregulation in young girls with Rett Syndrome during nighttime in‐home recordings

Abstract

This study was designed to specifically characterize the autonomic phenotype of cardiorespiratory dysregulation during the nighttime in young girls with MECP2 mutation-confirmed Rett Syndrome (RS), studied in their home environment. Computerized breath-to-breath and beat-to-beat characterization of at-home continuously recorded respiratory inductance plethysmography of chest/abdomen and ECG (VivoMetrics, Inc.) was obtained during overnight recordings in 47 girls with MECP2 mutation-confirmed RS and 47 age-, gender-, and ethnicity-matched screened controls (ages 2-7 years). We determined that although the breathing and heart rate appear more regular during the night compared to the day, young girls with RS demonstrate apparent nocturnal irregularities. Comparing daytime versus nighttime, breathing was more irregular, with an increased breathing frequency (and irregularity), mean amplitude of respiratory inductance plethysmography sum (AMP)/T(I), and heart rate and decreased AMP in girls with RS. Comparing girls with RS versus controls during nighttime recording, breathing was more irregular, with an increased breathing frequency (and irregularity), mean AMP/T(I), and heart rate. An increased uncoupling between measures of breathing and heart rate control indicates malregulation in the autonomic nervous system, and is apparent during the day as well as the night. This uncoupling may represent a mechanism that renders the girls with RS more vulnerable to sudden death.

A BDNF loop-domain mimetic acutely reverses spontaneous apneas and respiratory abnormalities during behavioral arousal in a mouse model of Rett syndrome

“…In light of the fact that breathing dysfunction in RTT patients improves with relaxation or sleep (Weese-Mayer et al, 2008; Katz et al, 2009; Ren et al, 2012; Ramirez et al, 2013), we considered the possibility that, rather than, or in addition to, any direct effects on respiratory control per se, LM22A-4 might also improve breathing by inducing sedation. Indeed, other studies have shown that apneic breathing in RTT mouse models is reduced by drugs with sedating or anxiolytic effects, including the GABA uptake inhibitor NO-711 (Abdala et al, 2010), the GABA A partial agonist L838,417 (Abdala et al, 2010), the 5-HT1A antagonist 8-OH-DPAT (Abdala et al, 2010), the benzodiazepines midazolam (Voituron and Hilaire, 2011) and diazepam (Abdala et al, 2010), the norepinephrine uptake inhibitor desipramine (Roux et al, 2007; Zanella et al, 2008), and the corticotropin-releasing hormone receptor 1 antagonist antalarmin (Ren et al, 2012).…”

The Integrative Role of the Sigh in Psychology, Physiology, Pathology, and Neurobiology

“…Various neurological conditions are associated with severe breathing disturbances. These disorders include multiple system atrophy (Schwarzacher et al, 2011), Rett syndrome (Ramirez et al, 2013b; Weese-Mayer et al, 2006, 2008b), Familial Dysautonomia (Carroll et al, 2012; Weese-Mayer et al, 2008a), sudden infant death syndrome (Garcia et al, 2013; Kinney et al, 2009; Paterson, 2013), congenital central hypoventilation syndrome (Ramanantsoa and Gallego, 2013), sleep apnea (Gozal and Kheirandish-Gozal, 2008; Ramirez et al, 2013a), Pitt Hopkins Syndrome (Gallego, 2012), and sudden death of epilepsy (Kalume, 2013; Sowers et al, 2013). Thus, understanding how breathing is generated within the nervous system and how the CNS controls ventilatory functions is of great clinical interest.…”

Circadian rhythm disruption in a mouse model of Rett syndrome circadian disruption in RTT

“…Sleep disruption is common in RTT patients (Glaze et al, 1987;Nomura, 2005;Young et al, 2007) with nighttime autonomic dysfunction also being reported later in the disease progression (Rohdin et al, 2007;Weese-Mayer et al, 2008). At least some of these sleep symptoms are disruptions in timing with RTT patients reporting difficulty sleeping at night and staying awake during the day, raising the possibility of an underlying circadian deficit.…”