Postural Neurocognitive and neuronal activated cerebral blood flow deficits in CFS

ramakentesh

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Another one from Dr Julian Stewart:

http://www.ncbi.nlm.nih.gov/pubmed/22180650

Postural Neurocognitive and Neuronal Activated Cerebral Blood Flow Deficits in Young Chronic Fatigue Syndrome Patients with Postural Tachycardia Syndrome.

Neurocognition is impaired in Chronic Fatigue Syndrome (CFS). We propose that impairment relates to postural cerebral hemodynamics. 25 CFS and 20 control subjects underwent incremental upright tilt at 0, 15, 30, 45, 60, and 75 with continuous measurement of arterial blood pressure and cerebral blood flow velocity (CBFv). We used an N-back task with N ranging from 0 to 4 (increased N= increased task difficulty) to test working memory and information processing. We measured N-back outcomes by the number of correct answers and by reaction time. We measured CBFv, critical closing pressure (CCP), and CBFv altered by neuronal activity (activated CBFv) during each N and every tilt angle using transcranial Doppler ultrasound. N-Back outcome in controls decreased with N but was independent of tilt angle. N-Back outcome in CFS decreased with N but deteriorated as orthostasis progressed. Absolute mean CBFv was slightly less than control in CFS at each angle. Activated CBFv in controls was independent of tilt angle and increased with N. In contrast, activated CBFv averaged 0 in CFS, decreased with angle and was less than control. CCP was increased in CFS suggesting increased vasomotor tone and decreased metabolic control of CBFv. CCP did not change with orthostasis in CFS, but decreased monotonically in control subjects, consistent with vasodilation as compensation for the orthostatic reduction of cerebral perfusion pressure. Increasing orthostatic stress impairs neurocognition in CFS. CBFv activation, normally tightly linked to cognitive neuronal activity, is unrelated to cognitive performance in CFS; increased CCP and vasomotor tone may indicate uncoupling of the neurovascular unit during orthostasis
 

Vitalic

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Am I correct in interpreting this as they started at a horizontal position and were gradually tilted upright? I've not had a tilt-table test carried out before so not sure how it works.
 

adreno

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Not really news to me, but the more studies on CFS/POTS, the better. Thanks for posting.
 

ramakentesh

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This one is interesting because ratehr than looking at what is happenng peripherally to blood flow in POTS it is looking at the cerebral consequences.
 

adreno

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This one is interesting because ratehr than looking at what is happenng peripherally to blood flow in POTS it is looking at the cerebral consequences.
It is well known already that POTS causes cerebral hypoperfusion. Here's an example:

Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H664-73. Epub 2009 Jun 5.
Decreased upright cerebral blood flow and cerebral autoregulation in normocapnic postural tachycardia syndrome.
Ocon AJ, Medow MS, Taneja I, Clarke D, Stewart JM.
Source

Department of Physiology, The Center for Hypotension, New York Medical College, Valhalla, New York 10532, USA.
Abstract

Postural tachycardia syndrome (POTS), a chronic form of orthostatic intolerance, has signs and symptoms of lightheadedness, loss of vision, headache, fatigue, and neurocognitive deficits consistent with reductions in cerebrovascular perfusion. We hypothesized that young, normocapnic POTS patients exhibit abnormal cerebral autoregulation (CA) that results in decreased static and dynamic cerebral blood flow (CBF) autoregulation. All subjects had continuous recordings of mean arterial pressure (MAP) and CBF velocity (CBFV) using transcranial Doppler sonography in both the supine supine position and during a 70 degrees head-up tilt. During tilt, POTS patients (n = 9) demonstrated a higher heart rate than controls (n = 7) (109 +/- 6 vs. 80 +/- 2 beats/min, P < 0.05), whereas controls demonstrated a higher MAP than POTS (87 +/- 2 vs. 77 +/- 3 mmHg, P < 0.05). Also during tilt, mean CBFV decreased 19.5 +/- 2.6% in POTS patients versus 10.3 +/- 2.0% in controls (P < 0.05). We then used a transfer function analysis of MAP and CFBV in the frequency domain to quantify these changes. The low-frequency (LF; 0.04-0.15 Hz) component of CBFV variability increased during tilt in POTS patients (supine: 3 +/- 0.9 vs. tilt: 9 +/- 2, P < 0.02). In POTS patients, there was an increase in LF and high-frequency coherence between MAP and CBFV, an increase in LF gain, and a lack of significant change in phase. Static CA may be less effective in POTS patients compared with controls, since immediately after tilt CBFV decreased more in POTS patients and was highly oscillatory and autoregulation did not restore CBFV to baseline values until the subjects became supine. Dynamic CA may be less effective in POTS patients because MAP and CBFV during tilt became almost perfectly synchronous. We conclude that dynamic and static autoregulation of CBF are less effective in POTS patients compared with control subjects during orthostatic challenge.

PMID:
19502561
 

ramakentesh

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That wasnt my point my good sir or madam.

And infact the study I printed above does NOT demonstrate that there is cerebral hypoperfusion, but rather that there is not a vasolidatory response to neuronal challenge as occurs in normal people. There is perhaps a loss of control of cerebral vasomotor or parasympathetic-mediated cerebral vasodilation.

Secondly that study you have printed doesnt actually demonstrate cerebral hypoperfusion - it demonstrates impaired cerebral autoregulation and thus lack of buffer of beat by beat blood pressure changes. There is sychronicity between blood pressure fluctuations in the peripheral and cerebral vasculature. This is in direct contrast to previously published work by Novak, et al.

Some more recent work by Stewart and Medows contradicts their earlier finding. In some patients there isnt dramatic blood pressure/cerebral synchronity and even very mild reductions in cerebral blood flow seem to cause dramatic alterations of consciousness in some POTS patients. Also postural hypocapnia is present in a subset, which is not hypoperfusion.

But feel please free to explain why there is alterations in neuronal control of cerebral vasodilation if you'd like.

Infact I wouldnt even suggest that cerebral hypoperfusion is an established fact in POTS. Studies on this are actually limited. Two groups found postural cerebral vasospasm, yet other groups suggest the opposite, and still others found normal cerebral vasulare responses. Most of this data has never been published or peer reviewed.
 

adreno

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It seems you are more on top of the finer intricacies of this phenomenon than I am. I stand corrected.
 

ahimsa

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Am I correct in interpreting this as they started at a horizontal position and were gradually tilted upright? I've not had a tilt-table test carried out before so not sure how it works.
I'm no expert but I have had a diagnostic tilt table test so I'll put in my two cents. :innocent1:

My test was nothing like this. My test had only two phases, one phase while lying flat (to get baseline measurements) and one phase while at 80 degree tilt (head up - some people get this part confused and think we're being turned upside down).

It might have included more phases (e.g., an IV of isoproternol or some such drug while the patient is tilted) but I passed out after 20 minutes just from the tilt alone, no drug needed.

25 CFS and 20 control subjects underwent incremental upright tilt at 0, 15, 30, 45, 60, and 75 with continuous measurement of arterial blood pressure and cerebral blood flow velocity (CBFv).
This study lists a whole range of tilt angles. This is lot more complicated than the tilt table test used to diagnose orthostatic intolerance (NMH and/or POTS). Plus they were also measuring different things, not simply heart rate and blood pressure. Perhaps someone who knows more can provide more details.
 

ramakentesh

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sorry that came across worse that it was supposed to - the danger of multitasking.

When I had my tilt test done they found a 42% reduction in carotid blood flow so for me at laest there was definaetly reduced cerebral blood flow. However the studies above are talking about alternative findings that account for the symptoms of abnormal cerebral blood perfusion.

I think the aim of the study was to see when or at what level of orthostatic stress the abnormal neuronal control of cerebral blood flow kicked in.
 
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Blimey, this is complicated.

I'm trying to reconcile this study with an earlier study by the same authors, also on CFS/POTS patients.

Both studies tested mental performance under tilt with the N-back test:
We used an N-back task with N ranging from 0 to 4 (increased N= increased task difficulty) to test working memory and information processing. We measured N-back outcomes by the number of correct answers and by reaction time.
Both studies found that while, unsurprisingly, test performance decreased as the test got more diffiuclt, the POTS/CFS patients performed worse than controls when tilted, but not when supine.

Both studies also looked at Cerebral Blood Flow velocity, CBFv, and both studies found no difference between patients and controls on this measure, eg from the first study:
Changes in CBFV were not different between the groups and were not associated with N-back scores.
However, the second study did find a difference between the groups when it looked at activated CBFv, defined as "CBFv altered by neuronal activity" (activated CBFv wasn't measured in the first study, AFAIK).
Activated CBFv in controls was independent of tilt angle and increased with N. In contrast, activated CBFv averaged 0 in CFS, decreased with angle and was less than control.
So if I've understood this correctly, the problem in CFS/POTS patients is not absolute CBFv but lack of regulation of activated CBFv, and this leads to (or is associated with) the decline in mental performance.
Maybe ramakantesh could check I have this right.:D
 

Dolphin

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However, the second study did find a difference between the groups when it looked at activated CBFv, defined as "CBFv altered by neuronal activity" (activated CBFv wasn't measured in the first study, AFAIK).

Activated CBFv in controls was independent of tilt angle and increased with N. In contrast, activated CBFv averaged 0 in CFS, decreased with angle and was less than control.
So if I've understood this correctly, the problem in CFS/POTS patients is not absolute CBFv but lack of regulation of activated CBFv, and this leads to (or is associated with) the decline in mental performance.
Maybe ramakantesh could check I have this right.:D
And just to be clear, the first study didn't investigate activated CBFv.

If people have both full texts, I would read the other one first as I think it gives a better explanation of what is involved with regard to the cognitive testing. Also, there is much less "biology". Then move on to this which will allow one to concentrate more on the biological mechanisms. (I think I pretty much understood this paper by doing it that way (just about or close to it) while I might have skimmed over some of the biology if I hadn't read the other paper first).
 

Dolphin

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I thought this was an interesting observation

Impaired N-Back Outcome in CFS/POTS during Orthostasis

Prior investigations have examined cognitive performance in CFS/POTS. While some studies
were performed supine, and sometimes while seated, posture was never altered. However, the
use of different positions (seated or supine) in prior studies could account for different results.
Thus Caseras (9) used a N=0 to 3 N-back task while performing supine BOLD fMRI. While they
found no N-back performance differences in CFS compared to control subjects similar to our
supine data of Figure 5, brain activation was reduced by 2-back and 3-back similar to our
findings in Figure 6. On the other hand cognitive deficits were not demonstrated by other
investigators using a variety of cognitive testing tools (13; 17). Most of these cognitive testing18
tools are unsuitable for time delimited orthostatic testing. Differences of CFS/POTS from control
appears to segregate with posture such that supine testing shows no difference in cognition
compared to control subjects when supine, but does show a difference in cognition compared to
control subjects while seated (14; 15; 59). This is consistent with orthostatic dependent results.
It is certainly possible. Whether the results of tests neatly divide up like this, I'm not sure.