NIH Research Roadmap Webinar (2023/2024)

[forestglip]

YouTube playlist with all of the webinar videos.

Nervous System
10:27 – Trisha Fisher - Lived Experience
19:56 – Gudrun Lange - Cognition
50:54 – Peter C. Rowe - Dysautonomia in ME/CFS
1:14:58 – Jonas Bergquist - The Neuroinflammatory Role in ME/CFS
1:57:30 – Jarred Younger - Neuroimaging
2:18:51 – Janet M. Mullington - The Problem of Non-Restorative Sleep in ME/CFS
2:55:50 – Peter Novak - Peripheral Nervous System

Immune System
5:21 – Nancy Klimas - Clinical Immunology of ME/CFS
1:00:02 – Carmen Scheibenbogen - Evidence for autoimmunity in ME/CFS
1:38:40 – Maureen Hanson - Immune cell-type approaches to identify mechanisms of ME/CFS
2:28:46 – Derya Unutmaz - Predictive and mechanistic insights into immune perturbations during ME/CFS
3:03:50 – Armin Alaedini - Gut-Immune-Metabolic Interplay in ME/CFS
3:25:57 – Angela Termini - Lived Experience
3:37:48 – Tracy Duvall - What my experience suggests for ME/CFS research

Metabolism
5:06 – Chris Wikman - Lived Experience of a Patient - Progress Made via Self-education, Determination, Self-tracking, and Analysis
17:08 – Shuzhao Li - The interplay between metabolism and immunology in ME/CFS
58:36 – Jessica Maya - Investigations and Consequences of Altered Metabolism in ME/CFS Immune Cells
1:20:49 – Jiabao Xu - Single-cell Raman technologies for diagnosis and investigation of ME/CFS immune cells
1:56:05 – Wenzhong Xiao - Studying Metabolomics in ME/CFS - A Computational Perspective
2:35:55 – Brent L. Williams - Microbial metabolism in ME/CFS pathogenesis: The state of supporting evidence and prevailing knowledge gaps
3:18:06 – Christopher W. Armstrong - Metabolic characterization of biofluids in ME/CFS

Genomics and Genetic Susceptibilities
7:44 – Hayla Sluss - Lived Experience
11:47 – Chris Ponting - Genetic risk factors of ME/CFS
49:54 – Steve Gardner - Combinatorial Analysis of Genetic Risk Factors for ME/CFS (and Long COVID) for UK Biobank
1:23:32 – Hanna M. Ollila -Genetic susceptibility in Long Covid and ME/CFS
1:35:38 – Anniina Tervi - Genetic correlations with ME/CFS
2:05:42 – Fereshteh Jahanbani, Varuna Chander - Characterizing the genetic basis of ME/CFS through case-control and family studies
2:35:27 – Alain Moreau - Contribution of Epigenomics to ME/CFS Pathogenesis: Past, Present and Future
3:05:39 – Kristina Allen-Brady - Key takeaways

Chronic Infections
4:59 – David Holcomb - Lived Experience - All in the Family (Caregiver)
16:34 – Michael Peluso - SARS-CoV-2 Persistence in the Post-Acute Phase of COVID-19
1:01:35 – Maureen Hanson - Chronic Infection in ME/CFS (other than herpesviruses)
1:51:09 – Anthony L. Komaroff - Herpesviruses in ME/CFS
2:31:59 – Simon R. Carding - HERVs & ME

Physiology
5:29 – Michelle James - Illuminating Whole Body Immune Responses In ME/CFS Using PET
29:22 – Robert K. Naviaux - ME/CFS and the cell danger response–the quest for a common denominator in complex disease
57:02 – Robert Phair - The Itaconate Shunt and ME/CFS: An Update
1:24:37 – Dominic Stanculescu - Overlapping Mechanisms in ICU and ME/CFS Patients
1:47:37 – Rebecca Robbins - Consensus report on what is refreshing sleep?
1:59:40 – Maiken Nedergard - Non-Refreshing Sleep
2:28:19 – Karl Johan Tronstad - Metabolism and ME/CFS
2:54:22 – Ronald W. Davis - ME/CFS & Long COVID, BH4 & NO
3:14:48 – Ludovic Giloteaux - Extracellular vesicles

Lesser Studied Pathologies
4:42 – Beth Pollack - Less Studied Pathologies
17:20 – Ilene Ruhoy - Connective Tissue Disorders, Spinal Conditions, and ME/CFS
1:20:07 – Anne Maitland - Mast Cell Activation Disease and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
1:48:16 – Julie Rehmeyer - Neurostructural conditions in ME/CFS and their interconnections with other comorbidities (Lived Experience)
1:58:20 – Laura A. Pace - Gastrointestinal Dysfunction in ME/CFS: The Role of the Neuroimmune Axis
2:30:07 – Beth Pollack - ME/CFS and Female Reproductive Health
2:39:37 – Natalie Thomas - ME/CFS and Neuroendocrinology
2:53:29 – Emelia von Saltza - Endometriosis & ME/CFS
2:59:05 – Roumiana S. Boneva, Elizabeth R. Unger - Reproductive Health in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Circulation
5:30 – Gwynn Dujardin - Lived Experience of ME: Circulation, Some History of "Science"
24:25 – Jane A. Mitchell - Endotheliitis
53:38 – Resia Pretorius - Thrombotic endothelialitis and microclots in Long-COVID & related conditions like ME/CFS
1:27:20 – Linda van Campen - Hypovolemia/blood volume
1:53:46 – Frans C. Visser - Orthostatic Intolerance: The role of cerebral blood flow and circulation
2:28:36 – Jiandi Wan - Impaired oxygen sensitivity of red blood cells from ME/CFS
2:59:06 – David M. Systrom - Neurovascular dysregulation during exercise

------

I'd like to slowly work my way through the NIH Research Roadmap webinar, creating summaries that I'll post in this thread as I go. I've already learned some interesting things in the first two talks, and I hope I can make easy to read summaries to get the main ideas for those who might not watch the videos. Note that these are not new videos - they were recorded in late 2023 to early 2024.

Let me know if you think the structure or content of these summaries could be improved.

Notes: Claims in the summaries are paraphrased from speaker's claims, and not necessarily verified by me. Any information I've added that was not provided by the speakers is placed in [brackets]. Summaries are not necessarily comprehensive of everything discussed, and may be more focused on things I think are most relevant to people with ME/CFS.

 

[forestglip]

19:56 – Gudrun Lange - Cognition

Main takeaways:

• Gudrun Lange, a neuropsychologist, explains that it is important to test cognitive function in ME/CFS studies, as this is one of the few symptoms which is objectively testable.
• Unfortunately, objective cognitive tests are not commonly included.
• Multiple studies, including a 2024 study Lange was a part of, have shown that ME/CFS does not cause problems in intelligence or strategizing without time limits.
• On the other hand, ME/CFS does appear to impact processing speed and memory.
• Many tests have low effect sizes or consistency, thus is it important to include validated tests, one example being the CogState Brief Screening Battery.
• Remote testing should be used when possible, as it includes patients who are not well enough to travel.

---------------------------------------------------

Gudrun Lange, a clinical neuropsychologist, discusses cognition problems and testing in ME/CFS.

“We know, pretty much, at this point, that [cognitive dysfunction] is there.” Mainly problems with complex and efficient information processing.

A 1999 study found that 89% of people with ME/CFS reported memory or concentration problems.(1) [The study was based on a random phone sample which was followed up with a physician diagnosis. It used Fukuda criteria.]

Cognitive dysfunction in ME/CFS is independent from depressive disorder.(2)

There are various commonly used patient reported outcome measures (PROMs) which include questions about cognitive function, such as DSQ, CDC-SI, and SF-36, but rarely used are PROMs specific to cognitive function, even though they are available.

Cognitive function is also rarely a primary outcome in trials, even though it is one of the few ME/CFS symptoms which can be objectively tested. Out of 52 trials from a 2020 review of ME/CFS RCTs, only 11 used an objective cognitive test, for example digit span or arithmetic test, as a primary outcome.(3)

A 2022 systematic review analyzed 33 case-control studies that used objective cognitive tests.(4) Several cognitive domains showed no difference between groups, including intelligence acquired over lifetime and strategizing without time constraints, which signals that it is unlikely that there is neurodegeneration involved. It is important to include intellectual measures such as these in studies, because lack of difference in these measures highlights magnitude of difference in other areas.

Several measures were inconsistent and unreliable for use as primary outcome measures, such as reaction times, motor coordination/speed, and finger tapping speed.

Domains with low variability between studies and at least moderate effect sizes included sustained and divided attention with speed component (multitasking), processing speed, and long term memory, for example with a focus on encoding/learning new information into memory. Generally, memory problems in ME/CFS differ from those in dementia.

Issues with cognitive testing:

• Often administered in a supervised clinical setting, so patient must be well enough to travel (travel may also increase fatigue and influence results.)
  • Around 10-15% of people with ME/CFS in the USA are housebound or bedbound and unable to travel, and thus are excluded from studies that use objective cognitive measures, even though these people are important beneficiaries of any potential treatments.
• When these tests are included, often measures are used which are brief and easy to administer, but have non-robust small effect sizes, for example digit span.

There are now cognitive batteries which can be done remotely. Comparisons of remote and in-clinic testing show that they produce similar results, including for measures highlighted above as robust for ME/CFS.

Lange helped lead a substudy of the CDC Multi-Site Clinical Assessment of ME/CFS (MCAM) study, which evaluated a remote cognitive battery in ME/CFS.(5) The CogState Brief Screening Battery (CBSB) was tested. Completion of the test took about 17 minutes.

The study found that there were no differences in accuracy measures, but significant differences in all measures involving speed.

A test of psychomotor speed (detection task, left) showed small but significant differences. This was used as a covariate to isolate the purely mental component of other tasks. The Groton Maze Learning task (right) was “very effective in finding differences between groups”.



[From paper:]

Both TWOB and GML tasks reflect increased cognitive complexity tapping into executive function and learning efficiency and necessitating a greater degree of mental multitasking. Both tasks were only administered at T0 and T1 in clinic as a remote administration option for these tasks had not been developed at the time of study enrollment. […] Group mean differences were clinically meaningful [...] to a moderate degree for GML-MPS, (T0: d = 0.6; T1: d = 0.7).

An NINDS/NIH resource exists which lists recommended common data elements in ME/CFS studies, including robust cognitive outcomes.

Spoiler: References

1. Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, et al. A community-based study of chronic fatigue syndrome. Arch Intern Med. 1999 Oct 11;159(18):2129–37.

2. Cockshell SJ, Mathias JL. Cognitive deficits in chronic fatigue syndrome and their relationship to psychological status, symptomatology, and everyday functioning. Neuropsychology. 2013 Mar;27(2):230–42.

3. Kim DY, Lee JS, Son CG. Systematic Review of Primary Outcome Measurements for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in Randomized Controlled Trials. Journal of Clinical Medicine. 2020 Nov;9(11):3463.

4. Aoun Sebaiti M, Hainselin M, Gounden Y, Sirbu CA, Sekulic S, Lorusso L, et al. Systematic review and meta-analysis of cognitive impairment in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Sci Rep. 2022 Feb 9;12(1):2157.

5. Lange G, Lin JMS, Chen Y, Fall EA, Peterson DL, Bateman L, et al. Cognitive assessment in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a cognitive substudy of the multi-site clinical assessment of ME/CFS (MCAM). Front Neurosci [Internet]. 2024 Nov 1 [cited 2025 Jan 19];18. Available from: https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1460157/full

 

[forestglip]

50:54 – Peter Rowe - Dysautonomia in ME/CFS

Main takeaways:

• Peter Rowe discusses dysautonomia in ME/CFS.
• There is mounting evidence that orthostatic intolerance (OI) plays a role in ME/CFS.
• Tilt testing in ME/CFS has shown measurable changes in immediate cognitive function, immediate subjective symptoms, as well as symptoms which last for days after testing.
• Blood flow in the brain (cerebral blood flow or CBF) decreases much more in ME/CFS than controls after changing to an upright position from lying down, even absent OI symptoms related to heart rate or blood pressure.
• Various other conditions might be associated with OI, including mast cell activation syndrome, craniocervical instability, and hyperhydrosis.
• Orthostatic intolerance is one of the most treatable aspects of ME/CFS, but further research is needed to develop better treatments and to learn about mechanisms.

--------------------------------------------------

Peter Rowe, a professor of pediatrics and the director of the Children’s Chronic Fatigue clinic at Johns Hopkins, talks about dysautonomia in ME/CFS.

Orthostatic tachycardia was first described in 1940 as causing symptoms such as exercise intolerance.(1) Four years later, its connection to a defect of blood returning to the heart (now called preload failure) was shown.(2)

One of Rowe’s early case-control pilot studies found that all participants with ME/CFS experienced worse fatigue after a tilt test, and most experienced lightheadedness, nausea, and warmth as well, while no controls reported any symptoms.(3) They later found that those with ME/CFS reported feeling unwell for days after the tilt test, but two liters of IV saline prevented symptom exacerbation, and even immediately improved their well-being.

A later study by another group found that the COMPASS questionnaire, which measures dysautonomia, not only shows a score difference between ME/CFS and controls, but also correlates with fatigue severity.(4)


A 2012 study of people with postural tachycardia syndrome (POTS) found that the tilt test caused objective decreases in cognitive function, as measured by the N-Back test.(5) A 2020 study that included Linda van Campen as an investigator produced a similar finding in ME/CFS.(6)


Another van Campen study showed that subjective concentration scores were decreased in ME/CFS up to seven days after tilt testing, but unchanged in healthy controls.(7)


The mechanism of symptoms in orthostatic intolerance appears to be due to reductions in blood volume and blood return to the heart, which subsequently cause decreased cerebral (brain) blood flow. This then causes a large increase in catecholamines and adrenal hormones. This can lead to any of these symptom states:

• Orthostatic hypotension (OH)
• Delayed orthostatic hypotension (dOH, symptoms after at least three minutes)
• Neurally mediated hypotension (NMH)
• Postural tachycardia syndrome (POTS)
• No change in HR or BP but other orthostatic intolerance symptoms

A study which tried to assess changes in cerebral blood flow (CBF) using transcranial doppler [uses ultrasound to measure velocity of blood in brain arteries] did not find any differences after tilt testing between ME/CFS and controls.(8)

But in 2018, van Campen et al showed that Doppler imaging of the arteries in the neck is sensitive enough to detect decreases in CBF after tilt testing in healthy volunteers.(9) They followed up with a large ME/CFS study (n=429 ME/CFS, 44 healthy controls) and found very significant differences between the two groups in CBF after tilt testing (p<0.0005), including in those with normal HR and BP responses after tilt testing (58% of the ME/CFS group). CBF was not different between groups while participants were lying down.


The degree of CBF change also correlated with the number of symptoms reported during tilt testing.


In 2023, van Campen et al looked at the relationship of heart rate (HR) to stroke volume index (SVI, volume of blood pumped per heart beat, adjusted for body surface area).(10) In healthy controls, a decrease in SVI during tilt testing leads to an increase in HR to compensate. The study showed that in ME/CFS, there was significantly less of an increase in HR to compensate for decreased SVI. This phenomenon has been termed chronotropic incompetence.

Dysautonomia/orthostatic intolerance is often seen alongside mast cell activation, joint hypermobility, vascular compression, and in some, neuroanatomic problems. Another van Campen study found that hypermobile ME/CFS patients had a significantly greater decrease in CBF than non-hypermobile.(11)


Several other studies are highlighted:

• POTS can occur in mast cell activation disorder (MCAS) (12)
• People with MCAS can have cardiovascular problems and symptoms similar to ME/CFS (13)
• A patient with a congenital spine issue recovered from severe POTS and ME/CFS after surgery (14)
• Pelvic vein compression issues may be associated with POTS. (15)

Orthostatic intolerance is one of the most treatable symptoms of ME/CFS. In 1995, Rowe’s lab showed that Florinef (fludrocortisone) led to dramatic, long lasting improvements in well-being in an unblinded study. (3) More effective medications have since become available.

What still needs to be done in regards to dysautonomia?

• Better orthostatic intolerance (OI) questionnaires
• More accessible OI testing
• Better identification of OI which is caused by structural issues (e.g. cervical stenosis, cranio-cervical instability, vascular compression), and which will thus not respond to medication

We still need to learn about the mechanisms of dysautonomia, including how genetics and infections play a role. Several potential causal mechanisms for POTS were proposed at an NIH meeting of clinicians and researchers(16), including:

• Absolute hypovolemia [low extracellular fluid] due to inadequate aldosterone release
• Cardiovascular deconditioning (though van Campen found no association between fitness and cerebral blood flow)
• Inflammation (e.g. mast cell activation)
• Excessive central sympathetic activation
• Auto-antibodies targeting circulatory system components
• Small fiber neuropathy [nerve issues] in lower limbs
• Connective tissue laxity (hEDS) allowing blood to pool

Does low cerebral blood flow lead to neuroinflammation? Do high catecholamines in OI affect immune system/infection susceptibility?

We need more research on treatments for orthostatic intolerance in ME/CFS, for example further studies of vasoconstrictors, volume expanders, drugs which decrease heart rate, and drugs which decrease catecholamine release/effect.

• Drugs for mast cell activation might help OI. Cromolyn helped a patient of Rowe’s who did not respond to any “conventional” OI treatments.
• Malcolm Brock and Frank Bosmans have seen clinical evidence of sodium channel blockers helping OI symptoms in some patients with comorbid hyperhidrosis. [One patient described in a paper: (17)]

It is important to carefully design trials in ME/CFS to account for symptom flares unrelated to treatment. Clear case definitions should be used to reduce heterogeneity. Large sample sizes will be needed, thus it is recommended to set up clinical trial networks.

Various trial designs may be useful, for example only randomizing those participants who report initial improvement to active and placebo groups.

Spoiler: References

1. MacLEAN AR, ALLEN EV. ORTHOSTATIC HYPOTENSION AND ORTHOSTATIC TACHYCARDIA: TREATMENT WITH THE “HEAD-UP” BED. Journal of the American Medical Association. 1940;115(25):2162-2167. doi:10.1001/jama.1940.02810510038010

2. MacLean AR, Allen EV, Magath TB. Orthostatic tachycardia and orthostatic hypotension: Defects in the return of venous blood to the heart. American Heart Journal. 1944;27(2):145-163. doi:10.1016/S0002-8703(44)90720-9

3. Bou-Holaigah I, Rowe PC, Kan J, Calkins H. The Relationship Between Neurally Mediated Hypotension and the Chronic Fatigue Syndrome. JAMA. 1995;274(12):961-967. doi:10.1001/jama.1995.03530120053041

4. Newton JL, Okonkwo O, Sutcliffe K, Seth A, Shin J, Jones DEJ. Symptoms of autonomic dysfunction in chronic fatigue syndrome. QJM. 2007;100(8):519-526. doi:10.1093/qjmed/hcm057

5. Ocon AJ, Messer ZR, Medow MS, Stewart JM. Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome. Clin Sci (Lond). 2012;122(5):227-238. doi:10.1042/CS20110241

6. van Campen CLMC, Rowe PC, Verheugt FWA, Visser FC. Cognitive Function Declines Following Orthostatic Stress in Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Neurosci. 2020;14:688. doi:10.3389/fnins.2020.00688

7. van Campen CLMC, Rowe PC, Verheugt FWA, Visser FC. Numeric Rating Scales Show Prolonged Post-exertional Symptoms After Orthostatic Testing of Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Med (Lausanne). 2020;7:602894. doi:10.3389/fmed.2020.602894

8. Razumovsky AY, DeBusk K, Calkins H, et al. Cerebral and systemic hemodynamics changes during upright tilt in chronic fatigue syndrome. J Neuroimaging. 2003;13(1):57-67.

9. van Campen CLMC, Verheugt FWA, Visser FC. Cerebral blood flow changes during tilt table testing in healthy volunteers, as assessed by Doppler imaging of the carotid and vertebral arteries. Clin Neurophysiol Pract. 2018;3:91-95. doi:10.1016/j.cnp.2018.02.004

10. van Campen CLMC, Verheugt FWA, Rowe PC, Visser FC. Orthostatic chronotropic incompetence in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). IBRO Neurosci Rep. 2023;15:1-10. doi:10.1016/j.ibneur.2023.04.005

11. van Campen MC, Rowe PC, Visser FC. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with Joint Hypermobility Show Larger Cerebral Blood Flow Reductions during Orthostatic Stress Testing Than Patients without Hypermobility: A Case Control Study. Published online 2021.

12. Shibao C, Arzubiaga C, Roberts LJ, et al. Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders. Hypertension. 2005;45(3):385-390. doi:10.1161/01.HYP.0000158259.68614.40

13. Theoharides TC, Valent P, Akin C. Mast Cells, Mastocytosis, and Related Disorders. New England Journal of Medicine. 2015;373(2):163-172. doi:10.1056/NEJMra1409760

14. Rowe PC, Marden CL, Heinlein S, Edwards CC. Improvement of severe myalgic encephalomyelitis/chronic fatigue syndrome symptoms following surgical treatment of cervical spinal stenosis. Journal of Translational Medicine. 2018;16(1):21. doi:10.1186/s12967-018-1397-7

15. Imaging findings of pelvic venous insufficiency in patients with postural orthostatic tachycardia syndrome - PubMed. Accessed January 19, 2025. https://pubmed.ncbi.nlm.nih.gov/32757696/

16. Vernino S, Bourne KM, Stiles LE, et al. Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1. Auton Neurosci. 2021;235:102828. doi:10.1016/j.autneu.2021.102828

17. Brock MV, Bosmans F. A MULTI-HIT MODEL OF LONG COVID PATHOPHYSIOLOGY: THE INTERACTION BETWEEN IMMUNE TRIGGERS AND NERVOUS SYSTEM SIGNALING. Trans Am Clin Climatol Assoc. 2024;134:149-164.

 

[Turtle]

Great summaries. Really helpful.
Maybe you could repeat the notes from the first post, now and then.
I would like to see more, in the speed of your own choosing.
But please take care of @forestglip first!!!

 

[rvallee]

“We know, pretty much, at this point, that [cognitive dysfunction] is there.” Mainly problems with complex and efficient information processing.

"This could have been an email" energy.

Good that they are cluing in on things we have told them for decades and are even part of the diagnostic criteria. Maybe by the 2040s they'll even start getting that it's post-exertional, not post-exercise. Maybe.

Probably not.

 

[forestglip]

Can someone explain how you can determine that symptoms persist for days because of a tilt test and not just being upright that day for the visit (or anything else about that day that was different)? Isn't it basically shifting a person from horizontal to vertical? So not much different from getting up after lying down. I'm assuming most were upright walking or in a wheelchair to get to the test.

Is it how long they are upright during tilt testing compared to a regular day?

One of the studies mentioned for prolonged concentration issues doesn't really go into any details that would answer my questions:
Numeric Rating Scales Show Prolonged Post-exertional Symptoms After Orthostatic Testing of Adults With [ME/CFS], van Campen et al, 2021

Edit: I mean you could isolate tilt testing through a different study design, but from this study it seems like it could have been anything about the day that could have caused worse concentration days later, but the paper says "Our data show that an orthostatic stressor is an important determinant of PEM."

Also, this is interesting: "No significant relation was found between CBF reduction and differences in NRS for pain, fatigue, or concentration (data not shown)."

 

[Turtle]

It's not just shifting from horizontal to vertical. The tilt table test takes away your coping mechanisms.
You're not allowed to wriggle your toes, as a soldier does on guard, that's a coping mechanism against OI.
The point of the test is that you are being moved in an upright position. Or 70 to 90 degrees.

My test lasted longer because my carotid artery splits into two parts just below the skull. It was difficult to place the doppler to get a good reading.
The machine had to be pinged, to make a marker.
After the test I stepped away but was left standing still. That was a big mistake, I think my head must have been quite low on oxygen for too long.
After my appointment I walked back to the station to travel for over 6 hours in an upright position, during covid lock down.
Enough room in an almost empty train, but because of covid I dare not lay down, Nothing was known about surfaces and virus back then.

Researchers don't mention this, but I will. I was told quite a few people get an emotional outburst during or right after the test.
Maybe @hibiscuswahine knows whether halting the coping machanisms can result in such an outburst? Can normal emotional control break in tilt table testing?
Why is this not mentioned by researchers as a possible side effect? Don't they trust us with this knowledge?

Could being low on oxygen cause PEM, I think so; but in my case the long travel time made it worse. I can't separate the two.

Every tilt table test should end horizontally for at least 10 minutes. Please claim that when tested.

 

[hibiscuswahine]

It's not just shifting from horizontal to vertical. The tilt table test takes away your coping mechanisms.
You're not allowed to wriggle your toes, as a soldier does on guard, that's a coping mechanism against OI.
The point of the test is that you are being moved in an upright position. Or 70 to 90 degrees.

My test lasted longer because my carotid artery splits into two parts just below the skull. It was difficult to place the doppler to get a good reading.
The machine had to be pinged, to make a marker.
After the test I stepped away but was left standing still. That was a big mistake, I think my head must have been quite low on oxygen for too long.
After my appointment I walked back to the station to travel for over 6 hours in an upright position, during covid lock down.
Enough room in an almost empty train, but because of covid I dare not lay down, Nothing was known about surfaces and virus back then.

Researchers don't mention this, but I will. I was told quite a few people get an emotional outburst during or right after the test.
Maybe @hibiscuswahine knows whether halting the coping machanisms can result in such an outburst? Can normal emotional control break in tilt table testing?
Why is this not mentioned by researchers as a possible side effect? Don't they trust us with this knowledge?

Could being low on oxygen cause PEM, I think so; but in my case the long travel time made it worse. I can't separate the two.

Every tilt table test should end horizontally for at least 10 minutes. Please claim that when tested.

I can only speculate on what may be going on, I would need to interview the person to discuss the emotions and how/if they related to the procedure. I did some reading on tilt tests and emotional outbursts has not been reported, perhaps in children due to fear and anxiety of the procedure.

It is important in the test to have a calm and comfortable surrounds - to have the most relaxed state of the autonomic system. This paper discusses all the requirements and is a good review of the tilt test and the environment needed.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8897774/

I have never had a tilt test only a NASA lean test which was uncomfortable, I do feel cognitively more slower and light headed but I am fortunate not to have the high heart rates of POTS or the nausea/presyncope symptoms (I have had the later as I had bouts of OH/low BP and pulse pressure but they have improved with electrolytes/compression wear). I prefer to move around when experiencing OI, I can get quite restless, it's an odd feeling. But optimally be lying flat or at least have my feet up. If I can't (masking for the public like in a GP's wait room), I would be crossing my legs/tensing my calves and toe wriggling. I also have interstitial cystitis and often need to pee so I am not sure how I would tolerate a tilt test as takes quite abit of time.

So if I could not do that i.e. the coping strategy, I can imagine during the procedure I would start feeling tense, not necessarily anxious, perhaps a bit irritable but talking to myself about staying calm. I would probably want to do some breathing (which is my preferred way to cope with unusual sensations/stressful situations) but perhaps one is not allowed to do that either as it does impact on the autonomic system. There is also the effect of preparing and going for the test, one's level of PEM etc.

I can see the potential for having an emotional outburst for various reasons, partially related to the individual, removal of normal coping strategies, the environment, the people present during the procedure etc, the challenge to the autonomic system, one's physiological state. I hope the staff present are receptive and understanding if emotional outbursts do occur.

Perhaps they should think about why it happens. Perhaps this is a common response in many people not just for pwME and they just see it as normal. I don't know. Is this part of poor cerebral perfusion on several different areas of the brain? Is it a frontal lobe symptom (disinhibition of emotions). The pathways are quite complex.

 

[Turtle]

I can only speculate on what may be going on, I would need to interview the person to discuss the emotions and how/if they related to the procedure. I did some reading on tilt tests and emotional outbursts has not been reported, perhaps in children due to fear and anxiety of the procedure.


Thanks very much for your research and help.
Maybe a tip for OI restless feelings. A mini-bike, two peddles on a small frame on the floor, just for a little spin and also cycling backwards. It can help the calve veins push up more blood.

For clarity, my reaction on the test came when I was back home. No need for you to return to work again (interview), I would not dare ask such a thing.
In my case not even the need for analyses. I did that myself. I just landed in a weird panic. I was insecure about the outcome of the test, had a normal TTT a decade earlier, result no OI.

I had read the research, about 20 times, that's how long it takes to get into my memory. The surroundings were as prescribed. Two things happened that were out of the ordinary. I had made an appointment for an ECG and my appointment was not with the doctor in front of me, no explanation was given. I had already left part of my fogged brain somewhere along the train track, assertivity must have been in that brain portion I left behind. I was already confused here.

After the intake I was strapped in for TTT, not ECG.
No real bad things happened during the test. I could take a few deep breaths lying down, which was not possible sitting all that time travelling and intake (with venous pooling my stomach can't protrude).
I was already back at the trainstation when I noticed that I had not had the ECG, but was too tired to go back to the clinic.

After my over 6 hours journey home I was exhausted from just sitting on my bum all day, from 4 am to 10 pm. During lockdown all trains stopped at every station, small country but lots of stations. And when I could put my head to rest, I panicked.
In no time I went from, no OI this time, no ME/CFS, no income, jobless, homeless. I saw myself on the pavement with all my belongings: and now what? Very weird.
I was a very small ball of misery. Panic, crying, sleeping, panic, crying, sleeping for two whole days.

After the second day my brain came back online and in a couple of minutes I knew; no OI didn't mean no ME/CFS. I would not loose my income. In my last job I gave information about social security, all the information I needed was there all along. I just could not access it. I was just a few years from retirement, they would not dare take my income away specially because last time I went to court over it and won.
I don't normally panic. But the TTT must have given me a knock on my head that made it into scrambled eggs.

I started researching. Hospitals that use a resting period after the test don't warn for headaches. Telling isn't it?
I needed to get my oxygen back to my head at the end of the test that's all. And certainly not standing still.
I asked the researchers to use that resting period too. To me it seemed a no-brainer to stop having no brain available. Too simple I suppose, I got no answer. "Specialists".

My last resort for help gone, I lost trust in the last specialists I trusted. That hurts a lot.

How can we get all tilt-table testers to use a resting period, 10 minutes will do, 20 minutes is even better. People with OI need it. I needed it too.

Sorry my post got so long. Mods feel free to move. I don't want to block forrestglip's great summary thread.

 

[ahimsa]

Isn't it [head up tilt testing] basically shifting a person from horizontal to vertical? So not much different from getting up after lying down. I'm assuming most were upright walking or in a wheelchair to get to the test.

Note: I have no medical background, these are just some comments from a patient who has orthostatic intolerance.

I can't provide the medical reason behind any of what happens, I can only share my own symptoms, plus a little bit that I've read from other patients or in papers I've seen online.

Patients can have very different reactions to tilt testing. If the person has no problems with dysautonomia or orthostatic intolerance then the tilt test probably won't be any worse than any other medical appointment. The biggest problem would be the exertion of getting there, communicating with doctors, etc.

At the other extreme there are some patients (I believe it is pretty rare) who have cardiac arrest or other heart problems from the tilt test. One person on this forum has mentioned that their "heart stopped" during a tilt test but I can't remember who that was.

More common is a reaction somewhere in the middle. For me the tilt table test was much worse than just "getting up after lying down." !!

The tilt test forces someone with orthostatic intolerance to stand still, and not move at all, for up to 40-45 minutes. This is very uncomfortable and can lead to fainting. That's what happened to me. In fact, I was subconsciously moving my feet (to keep from fainting!) and I didn't even realize it. The technician had to come over and tell me to stop moving. Less than a minute later (this was after about 20 minutes of standing) I fainted.

No isoproteronol was used, just being upright was enough to make me faint. After the tilt table test I crashed for about week, maybe a bit more.

I believe that the purpose of the tilt test is to stress the autonomic system. If your autonomic system is "working" then the test is not a problem.

If it's "not working" you will get symptoms during the test and will probably crash afterwards. Just like I get symptoms, and might crash later, after standing still in real life situations such as standing in line at a grocery store, or waiting for and then taking an elevator. That's why I now have a folding cane/seat so I don't have to stand in these situations.

The details of a "working" vs "not working" autonomic system are beyong my understanding!

I'm sure it's a lot more complex than just increased heart rate and/or dropping blood pressure (and fainting). I remember reading recent studies about cerebral blood flow - https://pmc.ncbi.nlm.nih.gov/articles/PMC7044650/ - but they are over my head.

Anyway, I hope this helps!

Edit: Sorry for any repeat of information that others have posted!