An attempt to explain the neurological symptoms of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, Wirth et al, 2021

[SNT Gatchaman]

An attempt to explain the neurological symptoms of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome
Klaus J. Wirth, Carmen Scheibenbogen and Friedemann Paul

Abstract
There is accumulating evidence of endothelial dysfunction, muscle and cerebral hypoperfusion in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). In this paper we deduce the pathomechanisms resulting in central nervous pathology and the myriad of neurocognitive symptoms. We outline tentative mechanisms of impaired cerebral blood flow, increase in intracranial pressure and central adrenergic hyperactivity and how they can well explain the key symptoms of cognitive impairment, brain fog, headache, hypersensitivity, sleep disturbances and dysautonomia.

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[SNT Gatchaman]

Conclusion

Neurological symptoms in ME/CFS can be severe and debilitiating, but no clear specific brain pathology or lesions have been detected so far. Whether neuroinflammation or a brain stem pathology exists—where dysautonomia may have its origin as the primary disturbance eliciting ME/CFS—remains to be shown.

Decreased CBF, disturbed local blood flow regulation and neurovascular coupling, central adrenergic hyperactivity, hypocapnia and increase in intracranial presssure seem to play a strong role in the pathophysiology of the neurological symptoms in ME/CFS.

They can well explain cognitive impairment, brain fog, headache, psychomotor slowing, ataxia and loss of coordination of movements, hypersensitivity, sleep disturbances and dysautonomia.

 

[SNT Gatchaman]

Endothelial dysfunction may play a role in the disturbance of neurovascular coupling. The question is whether the inflammatory mediators released from skeletal muscle can also affect neurovascular coupling, the local regulation of blood flow adjusting local perfusion to local neurophysiological activity. We think that influx of vasodilators, which otherwise also regulate local perfusion in other organs, into the cerebrovascular bed being under excessive vasoconstrictor influences via heightened sympathetic tone (stress), dysfunction of ß2AdR and endothelial dysfunction can only disturb a highly regulated fine tuning of vascular regulation and local blood distribution (neurovascular coupling).

A more recent finding is an increase in intracranial presssure based on neuroradiological signs in an MRI study. Signs of intracranial hypertension (IH) can be shown in 83% of the patients with ME/CFS. A further argument for a raised intracranial pressure is a higher prevalence of perineural or Tarlov cysts in the spinal cord in ME/CFS patients compared with healthy people.

 

[hibiscuswahine]

I especially like this quote “By the mechanisms outlined in our previous paper, ME/CFS, once fully established, is a state in which a high level of stress is maintained and fixed by a number of dysregulations and vicious circles, which the patient can hardly escape [40]. Since there is no recovery from stress in ME/CFS, α2-adrenergic autoreceptors and ß2AdR remain desensitized.

Good paper, really ties in some of the latest research into the cardiovascular system and pathways. I see intracranial hypertension is showing up in scans of long covid patients due to microclotting, if my recollection is correct.

@SNT Gatchaman what would be your personal opinion about routine MRI’s for PwME, this is not a standard investigation in NZ.

The hypocapnia explanation is very well explained and agree with their comments on sleep which clinically I have found very important.

 

[SNT Gatchaman]

Perineural cysts in the spine (Tarlov cysts) are clinically controversial. Radiologists usually note and dismiss as they were generally understood to be an incidental finding in scans performed for other reasons. Interestingly, more common in women and associated with connective tissue diseases. It may be that as a commonality in ME, they share the connective tissue link, rather than indicating raised intracranial pressure (or both). And of course again, the female predominance may explain their controversial clinical status.

I have little experience of symptomatic Tarlov cysts, except for some surprisingly large ones that had been "mis-interpreted" as ovarian cysts on ultrasound (there was no way to get this right with US alone), but I was impressed with their size.

Similarly, we see perivascular spaces in the brain commonly on MRI. Again it was usually a "mention and dismiss" in the report, or not even mention at all, as they are so common. While previously presumed incidental and asymptomatic, perhaps we will come to realise they are a marker of postviral/ME and related pathologies.

Neuroimaging by MRI would probably be most specific in the ME context when evaluating brainstem and other regions for neuroinflammation by advanced spectroscopy techniques. That's challenging and definitely not routine capability though and probably won't be for a while.

To try and answer your question, I don't think it's worth everyone jumping in for a standard brain MRI at this stage (conflict declaration - I have financial interest in patients having MRIs in NZ, so really I should be encouraging this!).

I think the best bang-for-buck, if we can hold off for a little longer until validated, is to wait for newer blood evaluations (fluorescent microscopy for micro-clots, cell markers and cytokines). To my mind, these hold the most promise and are upstream of eg brain changes on MRI. If the micro-clot findings hold together, there will suddenly be a rush for everyone trying to find them: for long COVID, ME / fibromyalgia etc and probably other diseases too. Ideally, automated blood analysers that can take a blood sample and say "micro-clots" will become available to handle what could end up being a large global load.

 

[SNT Gatchaman]

I especially like this quote “By the mechanisms outlined in our previous paper, ME/CFS, once fully established, is a state in which a high level of stress is maintained and fixed by a number of dysregulations and vicious circles, which the patient can hardly escape [40]. Since there is no recovery from stress in ME/CFS, α2-adrenergic autoreceptors and ß2AdR remain desensitized.

I also liked the idea that in this pathological state, orthostatic stress merely from sitting as the fundamental stressor, was enough to perpetuate symptoms. The context of doctors diagnosing patients with tachycardia as "having become anxious about standing up" reads less well after understanding this theory.