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An excerpt from a terrific article about a new finding by Jarred Younger, which finding is yet to be formally published.
Researchers have thought for decades that neuroinflammation is probably present in chronic fatigue syndrome (ME/CFS), but it’s only recently that the technology has been able to pick up the lower levels of neuroinflammation believed present in diseases like ME/CFS and fibromyalgia. The Japanese were the first to take a crack at it.
Neuroinflammation has long been thought to play a role in ME/CFS but only recently have the tools to study it become available.
They have long believed that inflammation produces central fatigue (fatigue emanating from the brain), which plays a major role in ME/CFS. In 2013, Watanabe proposed that inflammation in the brain was whacking the “facilitation system” which pops up when we are fatigued to boost signals from the motor cortex to keep our muscles moving. He also hypothesized that an inhibition system was turning up the fatigue in ME/CFS.
A 2016 study rounded the circle when it found evidence of reduced dopaminergic activity from a part of the brain (the basal ganglia) which activates the motor cortex. That fit in just fine with Miller’s results, which suggested that problems with the basal ganglia could be producing both the fatigue and the motor activity problems in ME/CFS.
The big breakthrough came in 2014 when the Japanese startled just about everyone with a PET scan study which found widespread neuroinflammation in the brains of ME/CFS patients. The study was small (n=19) but the findings appeared strong.
The neuroinflammation was widespread but was highest in the areas of the brain (thalamus, amygdala, midbrain, hippocampus) that had shown up in ME/CFS before. Plus, the Japanese were able to link specific regions of inflammation to specific symptoms. Inflammation in the thalamus was associated with cognitive impairment, fatigue and pain; inflammation in the amygdala was associated with cognitive issues; and inflammation of the hippocampus was associated with depression.
Anthony Komaroff called the findings the most exciting in decades. The Japanese began a much larger (n=120) neuroinflammation study. This year they published a large number of papers on ME/CFS in the Japanese Journal, “Shinkei Kenkyu No Shinpo” (Brain and Nerve). One of the papers was specifically on neuroinflammation but the findings have not yet been published in English journals.
Neuroinflammation – The Younger Way
Jarred Younger – who runs the Neuroinflammation, Pain and Fatigue Lab at the University of Alabama at Birmingham has also long believed that neuroinflammation plays a major role in chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM).
In 2015, he noted what a hot subject neuroinflammation had become. Seven years ago, he said, there was almost nothing on the microglia at the pain conferences. Now they’re loaded with presentations on microglia.
These immune cells are sensitive to so many factors and can be triggered in so many ways that virtually any stressor, from an infection to toxins to psychological stress, can potentially trigger a state of microglial sensitization in the right individual. With their ability to produce dozens of different inflammatory mediators, Younger believes that the difference between ME/CFS and FM could simply come down to small differences in how the microglia are tweaked.
Both diseases could be triggered by high rates of immune activation which, over time, sensitizes the microglia to such an extent that they start pumping out inflammatory factors at the first sign of a stressor.
New Non-Invasive Technique
Younger had just finished up his ME/CFS brain thermometry study. He used a new, less invasive way of assessing the brain called magnetic resonance spectroscopic thermometry (MRSt). The technique, which aims to create a thermometer for the brain, uses a magnetic resonance imaging (MRI) scanner. While Younger was assessing the temperature of the brain, he was also examining its chemical makeup.
My partner asked him how he glommed onto the heat mapping idea? It turned out that Younger had been trying for quite some time to find a non-invasive way to assess neuroinflammation. He needed a technique he could safely use again and again in his longitudinal (Good Day/Bad Day) studies.
None of the present techniques, however, fit the bill; they were all heavily invasive. The PET scan approach uses radiation to image the brain. Another approach using magnetized nano particles is supposed to be safe but it still requires putting little bits of metal into peoples’ brains…
After hitting several dead ends, he hypothesized that because inflammation produces temperature increases, he could try and create a heat map of the brain. Looking through the literature, he realized that thermometry was already being used in the brain to assess stroke and cancer patients. It turns out that the brain’s attempts to repair the damage from stroke and cancer results in huge temperature increases. The stroke and cancer researchers, though, were just focused on small areas of the brain.
Because Younger didn’t know exactly where in the brain to search in ME/CFS, that technique wouldn’t work for him. He had to develop a method that would produce a heat map and a chemical signature of the entire brain, and found a Florida researcher who developed a way to do that.
With this technique, it takes just 20 minutes in the machine to get an entire 3-D heat and chemistry map of an ME/CFS patient’s brain. After The Solve ME/CFS Initiative (SMCI) provided funding, he got to work and ultimately scanned the brains of 15 ME/CFS women and 15 age and sex matched healthy controls.
Widespread Neuroinflammation Found in ME/CFS Patients’ Brains
“The markers were truly elevated” Jarred Younger
It turned out that Younger’s brain-wide search technique was right on. Looking at single areas of the brain in ME/CFS patients would have produced misleading data. It turned out there was no single area or even a group of areas in the brain that were abnormal in ME/CFS: most of the brain was.
Younger found lactate – a product of anaerobic metabolism – widely distributed across the brains of people with ME/CFS. He opened a chart showing an amazing array of lactate-engorged brain regions. He picked out a few: the insula, hippocampus, thalamus, and putamen, which had particularly high levels. They were virtually the same regions the Japanese had found in their 2015 study. The fact that the temperature increases overlapped with the lactate increases provided further confidence that Younger had identified some key areas.
Check out the rest at Cort's blog:
https://www.healthrising.org/blog/2...mation-found-chronic-fatigue-syndrome-me-cfs/
Researchers have thought for decades that neuroinflammation is probably present in chronic fatigue syndrome (ME/CFS), but it’s only recently that the technology has been able to pick up the lower levels of neuroinflammation believed present in diseases like ME/CFS and fibromyalgia. The Japanese were the first to take a crack at it.
Neuroinflammation has long been thought to play a role in ME/CFS but only recently have the tools to study it become available.
They have long believed that inflammation produces central fatigue (fatigue emanating from the brain), which plays a major role in ME/CFS. In 2013, Watanabe proposed that inflammation in the brain was whacking the “facilitation system” which pops up when we are fatigued to boost signals from the motor cortex to keep our muscles moving. He also hypothesized that an inhibition system was turning up the fatigue in ME/CFS.
A 2016 study rounded the circle when it found evidence of reduced dopaminergic activity from a part of the brain (the basal ganglia) which activates the motor cortex. That fit in just fine with Miller’s results, which suggested that problems with the basal ganglia could be producing both the fatigue and the motor activity problems in ME/CFS.
The big breakthrough came in 2014 when the Japanese startled just about everyone with a PET scan study which found widespread neuroinflammation in the brains of ME/CFS patients. The study was small (n=19) but the findings appeared strong.
The neuroinflammation was widespread but was highest in the areas of the brain (thalamus, amygdala, midbrain, hippocampus) that had shown up in ME/CFS before. Plus, the Japanese were able to link specific regions of inflammation to specific symptoms. Inflammation in the thalamus was associated with cognitive impairment, fatigue and pain; inflammation in the amygdala was associated with cognitive issues; and inflammation of the hippocampus was associated with depression.
Anthony Komaroff called the findings the most exciting in decades. The Japanese began a much larger (n=120) neuroinflammation study. This year they published a large number of papers on ME/CFS in the Japanese Journal, “Shinkei Kenkyu No Shinpo” (Brain and Nerve). One of the papers was specifically on neuroinflammation but the findings have not yet been published in English journals.
Neuroinflammation – The Younger Way
Jarred Younger – who runs the Neuroinflammation, Pain and Fatigue Lab at the University of Alabama at Birmingham has also long believed that neuroinflammation plays a major role in chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM).
In 2015, he noted what a hot subject neuroinflammation had become. Seven years ago, he said, there was almost nothing on the microglia at the pain conferences. Now they’re loaded with presentations on microglia.
These immune cells are sensitive to so many factors and can be triggered in so many ways that virtually any stressor, from an infection to toxins to psychological stress, can potentially trigger a state of microglial sensitization in the right individual. With their ability to produce dozens of different inflammatory mediators, Younger believes that the difference between ME/CFS and FM could simply come down to small differences in how the microglia are tweaked.
Both diseases could be triggered by high rates of immune activation which, over time, sensitizes the microglia to such an extent that they start pumping out inflammatory factors at the first sign of a stressor.
New Non-Invasive Technique
Younger had just finished up his ME/CFS brain thermometry study. He used a new, less invasive way of assessing the brain called magnetic resonance spectroscopic thermometry (MRSt). The technique, which aims to create a thermometer for the brain, uses a magnetic resonance imaging (MRI) scanner. While Younger was assessing the temperature of the brain, he was also examining its chemical makeup.
My partner asked him how he glommed onto the heat mapping idea? It turned out that Younger had been trying for quite some time to find a non-invasive way to assess neuroinflammation. He needed a technique he could safely use again and again in his longitudinal (Good Day/Bad Day) studies.
None of the present techniques, however, fit the bill; they were all heavily invasive. The PET scan approach uses radiation to image the brain. Another approach using magnetized nano particles is supposed to be safe but it still requires putting little bits of metal into peoples’ brains…
After hitting several dead ends, he hypothesized that because inflammation produces temperature increases, he could try and create a heat map of the brain. Looking through the literature, he realized that thermometry was already being used in the brain to assess stroke and cancer patients. It turns out that the brain’s attempts to repair the damage from stroke and cancer results in huge temperature increases. The stroke and cancer researchers, though, were just focused on small areas of the brain.
Because Younger didn’t know exactly where in the brain to search in ME/CFS, that technique wouldn’t work for him. He had to develop a method that would produce a heat map and a chemical signature of the entire brain, and found a Florida researcher who developed a way to do that.
With this technique, it takes just 20 minutes in the machine to get an entire 3-D heat and chemistry map of an ME/CFS patient’s brain. After The Solve ME/CFS Initiative (SMCI) provided funding, he got to work and ultimately scanned the brains of 15 ME/CFS women and 15 age and sex matched healthy controls.
Widespread Neuroinflammation Found in ME/CFS Patients’ Brains
“The markers were truly elevated” Jarred Younger
It turned out that Younger’s brain-wide search technique was right on. Looking at single areas of the brain in ME/CFS patients would have produced misleading data. It turned out there was no single area or even a group of areas in the brain that were abnormal in ME/CFS: most of the brain was.
Younger found lactate – a product of anaerobic metabolism – widely distributed across the brains of people with ME/CFS. He opened a chart showing an amazing array of lactate-engorged brain regions. He picked out a few: the insula, hippocampus, thalamus, and putamen, which had particularly high levels. They were virtually the same regions the Japanese had found in their 2015 study. The fact that the temperature increases overlapped with the lactate increases provided further confidence that Younger had identified some key areas.
Check out the rest at Cort's blog:
https://www.healthrising.org/blog/2...mation-found-chronic-fatigue-syndrome-me-cfs/
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