A Thought Experiment on Muscles

Have another hot cross bun and an extra large glass of lemonade?

Well it’s all wonderfully confusing and interesting.

 

yes me too

it certainly is, I'm not keeping up with the thread never mind all the science on it, but I'm fascinated by it all even if i dont understand most of it. And its just so heartening to be reminded that so many brght minds are working on it! When i get so low i want to give up, i remind myself of this, & it gives me hope!

 

All this talk of afferent nerves & the spinal column... apologies if this is idiotic & totally unconnected scientifically but i wonder about the post mortem dorsal root ganglionitis findings & whether they have any connection or anything relevant to tell us?

I know the DRG are not part of the spinal chord, but arent they involved in sensory input/signalling too?

 

Absolutely, they are where the primary afferent neuron cell bodies are, with axons carrying on up the cord. So yes, I agree that the observations on DRG could be very important.

I recently went to a lecture on people who cannot feel pain and there is one form of the disease due to a genetic error in a gene that encodes for a long non-coding RNA that controls development of these cells. That would not be directly relevant to ME/CFS but it made me wonder whether in ME/CFS these cells are being changed by signals like LNC-RNAs that we wouldn't see or measure normally. `maybe only in very severe cases there might be a local cellular response of 'ganglionitis'.

 

I haven't managed to keep up on the whole discussion here, so please forgive me if this is out of scope.

I was wondering if there is indeed increase lactate buildup in pwME compared to HC?

And whether an intervention with beta-alanine has been looked into? It supposedly increases carnosine which has acid buffering abilities, to my understanding.

Seems like it also increases VO2max in healthy volunteers?
meta-analysis

 

Yes, that is kind of out of date.

Sidhu and Gandevia have made major contributions to the field and coincidentally have coauthored a review with Amann, which I strongly recommend anyone interested to read, including @Jonathan Edwards and @Simon M

"Critical considerations of the contribution of the corticomotoneuronal pathway to central fatigue"
https://www.researchgate.net/public...orticomotoneuronal_pathway_to_central_fatigue

MEPs are motor evoked potentials after a transcranial or cervicomedullary stimulus.

Note this depends on whether the motor unit pool was only partly or completely recruited during the tasks and hence the degree of motor units that are fatigued.

Large muscle groups can invoke larger reductions in motor cortex excitability due to having a greater number of feedback driving afferents. Which is important since this feedback mechanism is key to proper ventilatory regulation as metabolism becomes less efficient in those muscle groups. It is important to note that this increase in ventilation to compensate for fatiguing tasks is NOT driven by other types of CO2-induced chemoreceptor stimulation as found in this study: "Note the persistence of the hypoventilatory response in the presence of type III–IV afferent blockade – especially during mild and moderate intensity exercise – despite the presence of increased CO2-induced chemoreceptor stimulation." (https://pmc.ncbi.nlm.nih.gov/articles/PMC4578297/)


But this also begs the question about the persistence of this feedback post exercise - it persists longer than the fatiguing task itself even in healthy participants.

The problem I have with Walitt is they performed the TMS study inadequately.

Firstly, the use of 50% MVC isometric contractions of the Abductor pollicis brevis compared to a versus a dynamic/locomotor task because it doesn't generate the strong attenuation of the motor cortex due to afferent feedback because it is a minor muscle that does not consume that much oxygen even when working hard.

Secondly, they could have utilisied paired transcranial magnetic stimulation along with cervicomedullary magnetic stimulation so that they can contrast the corresponding differences in excitability in the motor cortex and the spine. Alterations in spinal excitability occur during fatigue due to the need of altering motor unit recruitment patterns as motor units fatigue. So their observed results may well be the result of afferent feedback in the spine, yet they concluded something very different.

They also fail to state their TMS methodology, such as the interstimulus interval. (eg short

Walitt fails to consider the most obvious answer: that the reduced voluntary drive can be because the participants are literally feeling a sensation of fatigue and reducing their output as a result. Walitt doesn't even consider this because he has already discarded all hypotheses that include the role of the peripheral afferents.

If Walitt bothered to read Amann 2022, the Deep phenotype manuscript would have a quite different conclusion, and if they read it before performing the experiment, then there might have been actual progress in the field.

 

I bet it would, because the afferent feedback is there still. But there is no way anyone is going to ethically set up EMS to lift 50kg on a leg machine.

I think JE is looking at it from a hypothesis generation point of view, but then again we could just explain it away with risk of EBV/CMV exposure and potentially a generalised hormonal risk factor in women.

Periodic paralysis can indicate other things - typically hypokalemia which can be due to adrenal insufficiency, kidney disease, thyroid overactivity etc.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11501104/

Yes! There are a few different related findings in addition to the autopsies that make for very curious suggestive evidence.

In certain cases I believe this IS the primary cause (damage and resulting sensitisation of afferent nerves). But it might be only in a minority rather than a majority of patients. Maybe in some severe cases in particular. That is one of the key findings that overlap between Guillain Barre Syndrome and ME/CFS that could explain why the former can lead to long-term symptoms that mimic the latter.

 

Gandevia probably not, Sidhu maybe.