The respiratory control of carbon dioxide in children and adolescents referred for treatment of psychogenic non-epileptic seizures

Abstract

Psychogenic non-epileptic seizures (PNES) are a common problem in paediatric neurology and psychiatry that can best be understood as atypical responses to threat. Threats activate the body for action by mediating increases in arousal, respiration, and motor readiness. In previous studies, a range of cardiac, endocrine, brain-based, attention-bias, and behavioral measures have been used to demonstrate increases in arousal, vigilance, and motor readiness in patients with PNES. The current study uses respiratory measures to assess both the motor readiness of the respiratory system and the respiratory regulation of CO2. Baseline respiratory rates during clinical assessment and arterial CO2 levels during the hyperventilation component of routine video electroencephalogram were documented in 60 children and adolescents referred for treatment of PNES and in 50 controls. Patients showed elevated baseline respiratory rates [t(78) = 3.34, p = .001], with 36/52 (69%) of patients [vs. 11/28 (39%) controls] falling above the 75th percentile (χ 2 = 6.7343; df = 1; p = .009). Twenty-eight (47%) of patients [vs. 4/50 (8%) controls] showed a skewed hyperventilation-challenge profile—baseline PCO2 <36 mmHg, a trough PCO2 ≤ 20 mmHg, or a final PCO2 <36 mmHg after 15 min of recovery—signaling difficulties with CO2 regulation (χ 2 = 19.77; df = 1; p < .001). Children and adolescents with PNES present in a state of readiness-for-action characterized by high arousal coupled with activation of the respiratory motor system, increases in ventilation, and a hyperventilation-challenge profile shifted downward from homeostatic range. Breathing interventions that target arousal, decrease respiratory rate, and normalize ventilation and arterial CO2 may help patients shift brain–body state and avert PNES episodes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00787-017-0976-0) contains supplementary material, which is available to authorized users.

Psychogenic non-epileptic seizures in children and adolescents: Part II – explanations to families, treatment, and group outcomes

“…Under task conditions, they showed an increased cortical response to an auditory stimulus (suggesting activation of brain arousal systems) ( Kozlowska, Melkonian, Spooner, Scher, & Meares, 2017 ) and increased motor readiness to emotion faces (suggesting activation of the motor system) ( Kozlowska, Brown, Palmer, & Williams, 2013 ). In the current cohort of 60 children/adolescents with PNES, in the baseline eyes-open, resting state-condition, we also found that our patients (vs controls) showed increased heart rates and increased respiratory rates ( Kozlowska, Rampersad, et al, 2017 ), consistent with the coupling between sympathetic arousal (which innervates the cardiac motor system) and the respiratory motor system. In one child in the sample, we also documented (via laryngoscopy) that the child activated an abnormally robust motor response in her larynx – adduction of the vocal chords – when she became frightened, distressed and highly aroused, resulting in cerebral hypoxia and a hypoxia-related non-epileptic seizure.…”

“…Limitations have been discussed in previous publications ( Kozlowska, Rampersad, et al, 2017 ) ( Kozlowska, Catherine, et al, 2017 ). An additional limitation in this study was the small number of patients ( n = 2) with intellectual disability.…”

Psychogenic non-epileptic seizures in children and adolescents: Part I – Diagnostic formulations

“…Other clinical characteristics, intelligence quotient, comorbid neurological conditions and the semiology of PNES are documented in Tables 2 and 3 . All children in the study participated in the PNES Hyperventilation Study, which provided neurophysiological data and HV-challenge profiles ( Kozlowska, Rampersad, et al, 2017 ). Eight children/adolescents were excluded from the previous study because of partial pressure of carbon dioxide (PCO 2 ) data were not collected, and four because PCO2 data were inadequate (technical difficulties or child’s lack of cooperation during the HV challenge).…”

“…We had also observed that many of our patients with PNES hyperventilated in and around the time of their PNES, and that HV appeared to trigger their PNES. We formally tested this hypothesis in the scientific arm of this study – the PNES Hyperventilation Study ( Kozlowska, Rampersad, et al, 2017 ). We found that nearly half of the children/adolescents with PNES (26 of 60) had difficulty in regulating CO 2 during a HV-challenge, and that over half those with PNES (32 out of 60) appeared to trigger their events with HV.…”

“…The PNES Hyperventilation Study indicated that HV was one of the mechanisms by which PFC function could be disrupted – triggering, in turn, PNES. HV can disrupt brain function and trigger PNES through two potential processes (see Kozlowska, Rampersad, et al, 2017 for review). In the first, cortical arousal phase of HV, it causes increased excitability in widely distributed networks and can therefore, via the arousal mechanisms, contribute to the functional failure of executive control circuitry (i.e.…”