I haven't yet watched the video but assume it links in with the study on ANS dysfunction at Newcastle University that is being funded by the MRC. There will be an update on this at the Research Collaborative conference in October.
MR/J002712/1
PI: Professor Julia Newton, Newcastle University
Title: Understanding the pathogenesis of autonomic dysfunction in chronic fatigue syndrome and its relationship with cognitive impairment
Start Date: 01/06/2012
End Date: 31/05/2015
Award Amount: £454,573.48
Lay Summary
Chronic fatigue syndrome (CFS) occurs in 0.2-0.4% of Europe's population, can affect all ages and currently its cause is unclear. Abnormality of the autonomic nervous system is recognised in over three quarters of those with CFS and is a plausible physiological mediator of the symptoms that are characteristic of CFS and fatigue in other chronic diseases. Autonomic nervous system dysfunction is characterised by symptoms of dizziness and lightheadedness when standing up, symptoms that we have shown to be present in nearly 90% of people with CFS, and the severity of which have been shown to predict the ability of CFS patients to function (more so than the severity of fatigue). Despite this, the mechanisms by which autonomic dysfunction arises in those with chronic fatigue syndrome are not understood and as a result treatments limited.
This study fills this gap by setting out to explore what leads to autonomic dysfunction in CFS using novel methodologies particularly whether it is upstream (related to abnormalities in centres in the brain that control the autonomic nervous system) or downstream (due to a peripheral volume or vascular problem) in origin. In non-CFS diseases autonomic dysfunction has also been shown to be associated with cognitive impairment. Over 80% of those with CFS describe problems with memory and concentration, so this study will also determine the relationship between autonomic dysfunction and these cognitive problems frequently found in those with CFS. Utilising the enormous resource created by this integrated study, the programme will look to develop diagnostic biomarkers.
The programme has two complementary phases: 1) an exploratory study that utilises ground breaking dynamic MR modalities that will allow study of brain function in CFS and how this relates to autonomic and cognitive function. 2) a downstream study which combines a number of work packages to define the relative contribution of cardiac and vascular function in autonomic dysfunction.
Understanding the mechanisms that lead to autonomic dysfunction in those with CFS will be a paradigm shift. This programme will lay a foundation for research by the applicant and others that will enable a future set of diagnostic tools, system based explanations of dysfunction, a new generation of therapies and ultimately clinical protocols that will counter the biological processes that underpin fatigue in a range of diseases.
This proposal will use state of the art techniques such as dynamic brain FMRI to measures cerebral blood flow during the autonomic nervous system stressor of the valsalva manoeuvre (considered to be a test of cerebral autoregulation) to understand the mechanisms that lead to autonomic dysfunction and the associated cognitive impairment seen in the majority of those with CFS.
This project will directly benefit patients through improving our understanding of how autonomic dysfunction arises in CFS and how it associates with cognitive function. This enhanced understanding will lead to the development of targeted appropriate treatments for clinical trials which will be aimed at reversing these abnormalities.
Technical Summary
Chronic Fatigue Syndrome (CFS) is a debilitating disease that can affect all ages and profoundly influences a sufferer's ability to function. Despite its impact, the cause of CFS remains unknown and there are no effective treatments. One consistent theme in the CFS literature is of compromise of the autonomic nervous system which has led to the concept that abnormality of regulation of the autonomic nervous system (autonomic dysfunction (AD)) underpins the pathogenesis and/or clinical expression of CFS. AD has been associated with cognitive impairment and risk of cognitive decline in non-CFS groups. Defining the pathogenesis of AD and its relationship with cognitive impairment would be of immense value for both the study of the pathogenesis and treatment of CFS, and the clinical management of fatigued patients.
Hypothesis Autonomic dysfunction in CFS arises dues to combination of central ('upstream') and peripheral ('downstream') abnormalities in blood pressure regulation. This leads to symptoms of brain hypoperfusion which is a cause of cognitive dysfunction. The aim of this study is to define the underlying physiological abnormalities that lead to autonomic dysfunction in CFS and its relationship with cognitive impairment.
Methodology Pathogenesis of AD will be determined using novel state of the art MR technologies developed for this application in CFS patients with an autonomic phenotype (with newly diagnosed and established disease) compared to CFS without autonomic phenotype and sedentary controls
Deliverables Having a comprehensive understanding of the pathogenesis of AD in CFS and its relationship with cognitive impairment will lead to targeted clinical trials that will improve autonomic symptoms, enhance functional ability and reduce cognitive impairment.
