Neuroendocrine and behavioural responses to CO2 inhalation in central versus peripheral autonomic failure

Abstract

Multiple system atrophy (MSA) and pure autonomic failure (PAF) represent distinct pathological models of autonomic failure in humans. We have investigated the neuroendocrine, behavioural and autonomic cardiovascular responses to the 35% CO2 challenge. Nine patients with MSA, nine with PAF and five control subjects received a single breath of 35% CO2. Peripheral autonomic failure (i.e., PAF) was associated with significantly lower resting noradrenaline levels. All groups demonstrated a significant pressor response to CO2. In controls, the mean pressor response was +60.2 mm Hg, which was significantly smaller in both the PAF (+26.8 mm Hg, P < 0.01) and MSA (+18.3 mm Hg, P < 0.001) patients. In addition, the onset of the response was significantly delayed in both MSA (140.2 s) and PAF (154.2 s) patients compared with controls (32.4 s, P = 0.04 and P = 0.03, respectively). Noradrenaline levels increased only in controls. Central autonomic impairment (i.e., MSA) was associated with lower cortisol release (+8.8% in MSA compared with +35.2% in control and +23.7% in PAF) and fewer somatic symptoms of emotional arousal. Both MSA and PAF exhibit marked sympathetic autonomic impairment, however, residual (albeit differing) sympathetic pathways can still maintain a partial cardiovascular response. A central autonomic lesion, however, also appears to be associated with blunting of both cortisol and emotional responses to this stress paradigm.

Autonomic and Cognitive dysfunction in Parkinson’s disease

“…In all our cases, dementia developed more than four years after onset of Parkinsonism. Thus, our population is different from that of patients with dementia with Lewy bodies (DLB), in whom dementia typically occurs within one year of onset of Parkinsonism [19]. The mean time interval between the onset of motor symptoms and the onset of dementia was 9.6 ± 3.4 years (range 6-16 years).…”

“…A relationship between autonomic failure, including OH, and neuropsychological dysfunction has been recently reported [16,19] This is an important issue, as there is evidence suggesting a bi-directional interactions between cognitive and autonomic process [15] and neurovascular instability, including OH, has been reported in neurodegenerative dementias [4]. It has been proposed that brain hypoperfusion in the setting of hypotension may result in subcortical ischemic vascular dementia [24].…”

Clinical characteristics of latent classes of CO 2 hypersensitivity in adolescents and young adults

“…However, the analysis of self-reported anxiety varies between peak anxiety (Wetherell et al, 2006), rate of anxiety increase during the task (Kaye et al, 2004), and the presence of a panic-like event (Kaye, Young, Mathias, Watson, & Lightman, 2006), which have all supported the associated of CO 2 hypersensitivity with anxiety disorders (Vickers et al, 2012). Moreover, the manifestation of anxiety and fear processes may be obscured by existing assessments of CO 2 hypersensitivity.…”

Effect of clinical autonomic dysfunction on cognitive functions in Parkinson’s disease

“…In another study, no association was found between the disease severity and orthostatic hypotension 21 . While there are studies which have not found an association between autonomic dysfunction and cognitive exposure 19,22 , there are also studies which show an association between the two 23 . Prospective studies are needed to show the association between autonomic dysfunction and cognitive exposure.…”