ME Hypothesis- Noradrenergic Neuron Dysfunction

Re the supermarket I was always the person that was running late or getting in there just before closing so it wasn’t the ambling for me. And it was always the checkout I collapsed at - although of course if I felt rubbish that was where I had to head and pass through (I think I’ve only ‘abandoned trolley’ a few times)

I’m aware of the irony of supermarkets being the exertion curve at the end because of the checking out then unpacking into car

but I suspect as I’ve had to be told in post offices to wait in a chair not the queue (after me looking ill and having to do so once) and gave up other eg clothes shopping before that (but at least there there are more places to sit or lie but further to get home if feeling awful) it’s just the standing , lights, exertion. But .. with the added barriers to getting to a chair you might have in other situations- they should add emergency chairs round the store or on trolleys.

 

I've heard a CGM is ore accurate than random fingersticks. How low did your sugar get? (If that's not too personal.)

 

Did it? I thought they only discovered correlation between the performance and DOPAC and DHPG in MECFS patients while there was no such correlation in healthy controls. In other words, low level of catechols didn't effect the performance in healthy people while it did in MECFS patients.

 

It would usually go to between 3mmol/l and 4mmol/l , never lower than 2.8mmol/l. There is a picture of my CGM chart at 18.48 in the video.

 

The endocrinologist I saw said that my hypos of 3.4 (or something) on my finger prick tests were not hypoglycemia because "in non-diabetic individuals, blood sugar levels under 2.5 mmol/L are considered hypoglycemic", I found this interesting because I had read otherwise...

 

They found norepinephrine correlated with time to failure, and cerebrospinal fluid DHPG, DOPAC and DOPA were all lower. There is a slide on the video that talks about the difference between healthy controls and ME at 9.43.

I actually think normetanephrine levels would be a good indicator of neuronal dysfunction as they may give a clearer indication of how much norepinephrine is being reuptaken. If norepinephrine levels are measured in CSF it might be measuring a persons COMT speed more than anything else.

 

Another irony is that stores can dump temporary displays anywhere that will nicely prevent wheelchair access, but chairs? No way: fire hazard. We weren't allowed to put them out, on pain of disciplinary action, in the public building where I worked for the same reason.

I doubt you'd get public liability insurance for a fold-down chair on a wheeled trolley, but the option to collect a lightweight folding one you could suspend from the trolley with hooks—great idea.

My nan had the best idea for Post Office queues. She took off her shoes, sat on the chair looking like an exhausted little old lady, and whoever joined the queue next would shove them forward with their foot until they got to the front. Thinking about the dates, she couldn't have been more than 55 when she started this oh-I'm-so-old-and-frail act.

 

Most CGMs are calibrated for key accuracy between the target set point of 5-8 , lower end ( 3 and lower) you need to check with a fingerprint. Higher than 15 the accuracy can tail off .
Based on Libre 2 .

 

It mostly came from my experiences of bad reactions to medications and the glucose issues. The researcher Karl Tronstad did a metabolic study showing 3 subtypes, and I have always been curious why some ME patients have POTS and some don't so I tried to come up with the most plausible explanation for that.

 

Except that the POT part of POTS may be something of a red herring, but nearly everyone would seem to have reduced cerebral blood flow on ortho-stress, regardless of normality or abnormality in the general cardiovascular system. So the symptoms may relate more to failures in the mechanisms of cerebral vascular regulation.

Regulation of cerebral blood flow in humans: physiology and clinical implications of autoregulation (2021, Physiological Reviews)

Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia: A quantitative, controlled study using Doppler echography (2020, Clinical Neurophysiology Practice)

The cardiac output - cerebral blood flow relation is abnormal in most ME/CFS patients with a normal heart rate and blood pressure response during a tilt test. (2024, Preprint: MedRxiv)

 

The reduced cerebral blood flow could have different causes. If someone has excessive vasodilation of blood vessels, blood can pool in the lower part of body and the blood flow to the brain is affected. However excessive cerebral vasoconstriction can reduce cerebral blood flow as well.

These differences may give us hints to differences between subtypes, although they could also be red herrings.

 

The blood pooling can be variable in an individual. I dont know if it is normal, but there are times when my son can lower his hands and you can see his veins begin to bulge then he raises them and they drain. The same with his feet & lower legs although they also become red very quickly. Then there are other times when this does not happen.