The effect of neurosurgical intervention and neurological damage on the perception of dyspnoea

Dyspnoea is a complex and unpleasant sensation that can have a severe impact on a person’s quality of life. Evidence for there being distinguishable types of breathlessness arising from distinct neural networks has been produced, and experimental models have also been produced to reproduce these sensations in healthy individuals. Current knowledge of the cerebral mechanisms has been gleaned predominantly through the use of brain imaging studies, however alternative methods also present opportunities to further elucidate the mechanisms behind intractable dyspnoea in ways that brain imaging cannot. Aim: The ultimate purpose of this thesis was to investigate the cerebral mechanisms behind breathlessness using neurological populations. Using deep brain stimulation (DBS), it is a primary aim of this thesis to further investigate the role of different brain structures in dyspnoea perception, specifically ‘air hunger’ which is a particularly unpleasant form of breathlessness often experienced by those with Chronic Obstructive Pulmonary Disease (COPD). An additional aim was to investigate whether neurological damage in the form of Parkinson’s disease, and glioma of the insular cortex alters the perception of breathlessness. Methods: (i) Experimental air hunger was induced in participants with deep brain stimulation of the motor thalamus to assess whether perception of dyspnoea is changed when stimulation is turned ON compared to when it is turned OFF. Experimental air hunger was also induced in one patient with low grade glioma to explore the impact of this damage on the insular cortex. (ii) A validated tool for measuring breathlessness called the Dyspnoea 12 questionnaire was utilised in patients who were breathless at rest and whom had DBS of the motor thalamus or the STN. This questionnaire was completed with their stimulation turned ON and turned OFF. This same questionnaire was also used to assess dyspnoea in individuals in the community with Parkinson’s disease to determine the prevalence of dyspnoea in this group (iii) Local field potentials (LFPs) where recorded from the motor thalamus whilst air hunger was induced. These LFPs are signals which correlate with neural activity. Results: (i) Participants with DBS of the motor thalamus rated air hunger significantly lower with stimulation ON in comparison to OFF by (median change 12mmVAS; range +19 to -50mmVAS). (ii) The participant with low grade glioma of the insular cortex did not rate an increase in breathlessness when air hunger was experimentally induced (increase in PCO2 of 11mmHg with VE fixed at 4.4 L/min). (iii) Participants with breathlessness at rest and DBS of the STN reported an overall increase in breathlessness when stimulation was turned on (an increase of 10% fullscale in the D12 total score). Conversely, DBS of the motor thalamus in participants with breathlessness at rest due to pre-existing COPD experienced a reduction in breathlessness with stimulation ON (-20.2% full scale for D12 total score) (iv)The prevalence of dyspnoea in individuals with Parkinson’s disease was 63.6%. (v) an LFP signal was detected when air hunger was induced that was not present in other breathing conditions. Conclusions: The motor thalamus and the STN have opposite roles in modulation of breathlessness, the mechanism of which is yet to be determined. The prevalence of breathlessness among patients with Parkinson’s disease is considerable and warrants more attention. Glioma of the insular cortex confirms the importance of this region in breathlessness perception. Study of patients with neurological interventions (Deep brain stimulation) and with neurological damage (low grade glioma or Parkinson’s disease) will lead to a better understanding of the cerebral network for dyspnoea perception and ultimately to identify new treatment options for intractable dyspnoea.

Grantor dc:publisher

Oxford Brookes University

Year dc:date

2020

Author dc:creator

• Golding, Charlotte Georgia

Contributors dc:contributor

• Moosavi, Shakeeb
• Green, Alex

Statement dc:rights

• All rights reserved

Language dc:language

en

DOI dc:identifier

https://doi.org/10.24384/v0ww-9543

OAI identifier oai:identifier

tle:3cc158d9-d3cf-40d7-bd48-5a19ddea64bc:d6bd9758-527a-46cd-bfe2-c433766e8fca:1