Make Visible: Understanding Complex Illness

Amy Arnsten, PhD, is a Professor of both Neuroscience and Psychology at Yale University, where she runs her own lab which studies and teaches about the brain’s higher cortical circuits and their molecular regulation. In this week’s episode we discuss Prof. Arnsten’s recent paper published in Biological Psychiatry looking at the impact of stress (both physical and mental) and inflammation on the prefrontal cortex, an area of the brain with implications in a range of conditions from depression and schizophrenia, to Alzheimer's and Long Covid. Arnsten explains how she and her lab are able to observe the biological changes that take place in the brain when under chronic stress, or triggered by inflammation, which can lead to a primitive survival response: shutting down higher cognitive functions.  This area of the brain is responsible for the regulation of our emotions, our mood and our behaviour.  Changes in this region lead to the brain fog, memory issues and emotional dysregulation that is prevalent in these disorders. And she talks us through the pathway of kynurenic acid production, levels of which are elevated in conditions such as Long Covid which inhibits neurotransmission.  The understanding of this could lead to break-throughs in our diagnosis and treatment of such conditions.  And Prof. Arnsten is already seeing promising potential with guanfacine, a compound that her lab developed for the treatment of ADHD (approved by the FDA in 2009).  A combination of guanfacine, which strengthens connections in the prefrontal cortex, with the anti-inflammatory, antioxidant supplement NAC (N-acetyl cysteine) seems to show possible beneficial applications in Long Covid.

Lucinda Bateman, M.D. has been seeing patients, learning about, and educating about ME/CFS and fibromyalgia for decades. She is Chief Medical Officer of the Bateman Horne Center, Salt Lake City, whose mission is “improving access to informed health care for individuals with ME/CFS, Long COVID, and fibromyalgia by translating clinical expertise into medical education and research initiatives”. Dr. Bateman was one of the researchers responsible for the National Academy of Medicine’s 2015 report on ME/CFS, a seminal paper that helped define the diagnostic criteria for ME / CFS.  Since then she has authored innumerable papers, working with the CDC alongside many of the stalwarts of the chronic illness medical community as part of the longitudinal multi-centre (MCAM) research that has looked at the impact, treatment protocols and drivers of ME/CFS. A member of the ME/CFS Clinican Coalition, she is dedicated to advancing understanding of these chronic conditions and improving care and outcomes for patients.  Her work has found many benefits from treating co-morbidities in chronic illness, such as POTS, with her most recent publication addressing chronic overlapping pain conditions, including fibromyaligia, that are regularly found alongside ME/CFS. And since the inception of Long Covid her work has pivoted to include this new heterogenious group of post-infection patients.  Much of her recent work has been looking at the parallels and differences between these illnesses and applying her historic knowledge to this new disease: she is one of the ME/CFS and Long Covid specialists working with the NIH on the RECOVER program. And her deep understanding of post- exertional malaise once again highlights the importance of pacing across these conditions Her work over the decades has been tireless to developing understanding of, and treatment paradigms for, chronic post-infectious syndromes.

In this week’s episode renowned cardiologist Dr. Boon Lim returns for Part 2 of the conversation with Emily Kate Stephens, presenting three clarifying analogies to represent a wider view of the impact of acute stress on the autonomic nervous system, and its role in complex chronic illness. Dr. Boon Lim uses the poem The Blind Man and the Elephant to exemplify the need for us and our medical practioners to approach chronic illness by looking at the body and mind as a whole rather than individual parts.  He describes the body affected by Long Covid as a factory for which we need to find the off-switch.  And he sets out the image of a gazelle in long grass: constantly on high alert anticipating attack, as a way for us to understand the way in which our bodies have been pushed into chronic stress. Dr Lim explains the way in which returning to homeostasis requires balancing of our sympathetic and parasympathetic systems and the consequences of imbalance.  He calls for us to consider the idea of stress reduction for alleviating some of the negative consequences of post-viral illness and we discuss the power of the breath, mindfulness and acceptance, not simply as a way to calm the mind, but to influence the entire body and nervous system. Dr Lim is able to demonstrate the scientific basis for what some might consider to be more esoteric ideas, discussing the ENO’s Breathe Programme, which carried out one of the first RCTs performed in Long Covid, alongside the way in which HRV monitoring can show the changes driven by such strategies.  Despite his heavily medical credentials, Dr Lim endeavours to grasp the mental and emotional aspects of chronic illness, whilst highlighting the importance of collaboration between patients and healthcare providers to achieve progress. The books discussed in this episode were: Johann Hari's -  "Stolen Focus: Why You Can't Pay Attention" James Nestor's - "Breath: The New Science of a Lost Art" Make Visible @visible_health @visible.health

Director for the Center for Healthy Aging Research at the Rutgers Institute for Health, Dr William Hu is a cognitive neurologist: he studies and treats patients whose thinking is affected by disease. Typically Dr Hu was dealing with Alzheimer's and related dementias in patients who were cognitively ageing whilst otherwise healthy, and those whose cognition was affected by their illness such as HIV or MS.  But since the Covid pandemic began, Dr Hu started seeing large numbers of patients whose ‘brain fog’ was sufficiently severe that they suspected they had early onset Alzheimer's, along with those who knew that their cognition, memory and thinking had demised to a degree that they were aware of it, but standard testing was inconclusive. In this week’s episode we discuss the way in which Hu and his team at Rutgers used brain imaging and analysis of cerebrospinal fluid (CSF), which enabled them to identify changes in the brain of patients with brain fog.  Their study, published in Cell, revealed that they could see that these patients had the markers of persistently activated immune function in the brain.  Whilst they were unable to detect SARS CoV-2 virus in the CSF, their findings correlate with the theory that those with Long Covid have viral persistence, and they were also able to see that this brain activation was no longer present in those that recovered. We talk through the implications of these findings for treatment and research into other chronic conditions, and discuss methods that might assist the immune system in recovering from these cognitive impairments and alleviate symptoms.  And reassuringly, Hu’s ideas involve trials in treatments that already have FDA approval for other conditions, meaning perhaps resolution is not so far out of reach. Make Visible @visible_health @visible.health