Post-Exertional Malaise - Neurobiological Changes - Video 6 of 7

Post-Exertional Malaise (PEM) in ME-CFS: The video discusses the neurobiological changes observed in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), particularly during episodes of post-exertional malaise.

Microglial Activation: In ME/CFS, microglia or microglial cells, which are a type of brain cell, transition from a resting state to a pro-inflammatory state.
Cytokine Storm: These activated microglial cells release proinflammatory cytokines, including IL-6, TNF-alpha, and interleukin-1-beta.
Sickness Response: The presence of these cytokines in specific brain regions can lead to a "sickness response" characterized by symptoms such as heavy fatigue, brain fog, confusion, malaise, and low motivation.
Comparison with Healthy Individuals: In healthy people, this Cytokine Storm is a temporary process, often during active infections. However, in ME/CFS patients, microglia cells might remain activated or rapidly switch between states.

Elevated Lactate: Magnetic resonance spectroscopy detected lactate levels in ME/CFS patients' brains that were 4x higher than in controls. Elevated lactate indicates neurons running out of glucose, leading astrocytes to produce lactate as an alternate energy source.
Significance of Lactate: High brain lactate is rare and usually linked to significant vascular or malignant pathology.
Choline Levels: Vitamin B4 (Choline), indicating high neuronal cell tissue turnover, was found to be particularly elevated in the left anterior cingulate cortex of ME/CFS patients.
Brain Thermometry: This technique revealed that ME/CFS patients' brains were about 1 degree hotter than controls, suggesting a high metabolic demand.

PET Scans: Positron emission tomography (PET) scans were used to measure TSPO levels, a marker for activated microglia. Elevated TSPO levels were found in regions like the thalamus, cingulate, and hippocampus.
Correlation with Lactate: The same brain regions with elevated TSPO levels also showed high lactate levels in MR-spectroscopy studies.
Default Mode Network (DMN): The DMN, a network of brain regions that activate when the brain is at rest, showed abnormal patterns in ME/CFS patients.
- BOLD Scans: These scans evaluated the DMN and found lower resting neurological activity in all posterior nodes of this network in ME/CFS patients.
- Medial Prefrontal Cortex: After exercise, this region showed increased activity in ME/CFS patients compared to before exercise, suggesting an uncoupling from the rest of its neuronal network. This abnormal activation might be a pathological consequence of exercise in ME/CFS patients.

Research & Support: The video is part of a series funded by the OMF-funded Medical Education Resource Center (MERC) at BHC and emphasizes the importance of continued research and donations to maintain public access to such educational resources.

Microglial Cells:

Microglial cells are a type of cell found in the brain and spinal cord. Think of them as the "clean-up crew" or "security guards" of the nervous system. They monitor the health of brain cells and respond to any signs of injury or disease. When they detect a problem, they can become activated to clean up debris or fight off harmful agents.

Proinflammatory Cytokines:

Cytokines are small proteins that cells release to communicate with each other. They play a role in cell signaling, helping to coordinate the body's response to different situations.
"Proinflammatory" means that these cytokines promote inflammation, which is the body's way of responding to injury or disease. Inflammation can be protective, but if it's excessive or prolonged, it can cause harm.
IL-6, TNF-alpha, and interleukin-1-beta are specific types of cytokines. When released in large amounts, they can cause symptoms like fatigue, fever, and pain.

Lactate Levels:

Lactate is a chemical compound produced in the body, especially during intense physical activity when there's not enough oxygen to produce energy in cells. It's often associated with muscle fatigue.
In the context of the brain, elevated lactate levels are unusual. The brain primarily uses glucose (a type of sugar) for energy. If neurons (brain cells) run out of glucose, they might resort to other sources of energy, leading to increased lactate production.
When the video mentions that lactate levels in ME/CFS patients' brains were "4x higher than in controls," it means that these patients had four times the amount of lactate in their brains compared to healthy individuals, suggesting some abnormal metabolic activity.

Choline Levels:

Choline is a nutrient that's vital for several bodily functions, including brain development and nerve function.
In the context of brain imaging, elevated choline can indicate increased cell membrane turnover or cell damage. When the video mentions elevated choline in the brains of ME/CFS patients, it suggests that there might be increased cell activity or damage in certain brain regions.