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Cortical Processing of Respiratory Occlusion Stimuli in Children with Central Hypoventilation Syndrome

¹ The Sleep Center, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; ² Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania; ³ Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; ⁴ SRI International, Menlo Park, California; and ⁵ Department of Psychology, The University of Melbourne, Parkville, Victoria, Australia

Correspondence and request for reprints should be addressed to Ian M. Colrain, Ph.D., SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025. E-mail: ian.colrain{at}sri.com

Rationale: The ability of patients with central hypoventilation syndrome (CHS) to produce and process mechanoreceptor signals is unknown.

Objectives: Children with CHS hypoventilate during sleep, although they generally breathe adequately during wakefulness. Previous studies suggest that they have compromised central integration of afferent stimuli, rather than abnormal sensors or receptors. Cortical integration of afferent mechanical stimuli caused by respiratory loading or upper airway occlusion can be tested by measuring respiratory-related evoked potentials (RREPs). We hypothesized that patients with CHS would have blunted RREP during both wakefulness and sleep.

Methods: RREPs were produced with multiple upper airway occlusions and were obtained during wakefulness, stage 2, slow-wave, and REM sleep. Ten patients with CHS and 20 control subjects participated in the study, which took place at the Children's Hospital of Philadelphia. Each patient was age- and sex-matched to two control subjects. Wakefulness data were collected from 9 patients and 18 control subjects.

Measurements and Main Results: During wakefulness, patients demonstrated reduced Nf and P300 responses compared with control subjects. During non-REM sleep, patients demonstrated a reduced N350 response. In REM sleep, patients had a later P2 response.

Conclusions: CHS patients are able to produce cortical responses to mechanical load stimulation during both wakefulness and sleep; however, central integration of the afferent signal is disrupted during wakefulness, and responses during non-REM are damped relative to control subjects. The finding of differences between patients and control subjects during REM may be due to increased intrinsic excitatory inputs to the respiratory system in this state.

Key Words: central hypoventilation syndrome • respiratory-related evoked potentials • wakefulness • sleep

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Central hypoventilation syndrome is a rare disease characterized by generally adequate breathing during wakefulness but hypoventilation during sleep. Previous studies suggest that people with this syndrome have compromised central integration of afferent stimuli. What This Study Adds to the Field In patients with central hypoventilation syndrome, integrated processing of the respiratory stimuli is disrupted during wakefulness, and responses during non-REM are damped relative to responses of control subjects.