Tag: cerebral blood flow velocity

Phenylephrine Alters Phase Synchronization between Cerebral Blood Velocity and Blood Pressure in Chronic Fatigue Syndrome with Orthostatic Intolerance

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) with orthostatic intolerance (OI) is characterized by neuro-cognitive deficits perhaps related to upright hypocapnia and loss of cerebral autoregulation (CA). We performed N-back neurocognition testing and calculated the phase synchronization index (PhSI) between Arterial Pressure (AP) and cerebral blood velocity (CBV) as a time-dependent measurement of cerebral autoregulation in 11 control (mean age=24.1 years) and 15 ME/CFS patients (mean age=21.8 years). All ME/CFS patients had postural tachycardia syndrome (POTS).

A 10-minute 60⁰ head-up tilt (HUT) significantly increased heart rate (109.4 ± 3.9 vs. 77.2 ± 1.6 beats/min, P <0.05) and respiratory rate (20.9 ± 1.7 vs. 14.2 ± 1.2 breaths/min, P < 0.05) and decreased end-tidal CO2 (ETCO2; 33.9 ± 1.1 vs. 42.8 ± 1.2 Torr, P < 0.05) in ME/CFS vs. control. In ME/CFS, HUT significantly decreased CBV compared to control (-22.5% vs -8.7%, p<0.005).

To mitigate the orthostatic CBV reduction, we administered supplemental CO2, phenylephrine and acetazolamide and performed N-back testing supine and during HUT. Only phenylephrine corrected the orthostatic decrease in neurocognition by reverting % correct n=4 N-back during HUT in ME/CFS similar to control (ME/CFS=38.5±5.5 vs. ME/CFS+PE= 65.6±5.7 vs. Control 56.9±7.5). HUT in ME/CFS resulted in increased PhSI values indicating decreased CA. While CO2 and Acetazolamide had no effect on PhSI in ME/CFS, PE caused a significant reduction in PhSI (ME/CFS=0.80±0.03 vs ME/CFS+PE= 0.69±0.04, p< 0.05) and improved cerebral autoregulation. Thus, PE improved neurocognitive function in ME/CFS patients, perhaps related to improved neurovascular coupling, cerebral autoregulation and maintenance of CBV.

Source: Medow MS, Stewart JM. Phenylephrine Alters Phase Synchronization between Cerebral Blood Velocity and Blood Pressure in Chronic Fatigue Syndrome with Orthostatic Intolerance. Am J Physiol Regul Integr Comp Physiol. 2024 Apr 29. doi: 10.1152/ajpregu.00071.2024. Epub ahead of print. PMID: 38682242. https://journals.physiology.org/doi/abs/10.1152/ajpregu.00071.2024 (Full text available as PDF file)

Head-down tilt reduces the heart rate in postural tachycardia syndrome in acute setting: a pilot study

Abstract:

Background: Reduced preload and thoracic blood volume accompany postural tachycardia syndrome (POTS). Head-down tilt (HDT) increases both preload and intrathoracic blood volume. The objective of this study was to assess the safety and efficacy of HDT in POTS in acute settings.

Methods: This retrospective study evaluated POTS patients. Analyzed data included heart rate, blood pressure, cerebral blood flow velocity (CBFv) in the middle cerebral artery, and capnography. The baseline supine hemodynamic data were compared with the data obtained at the second minute of the -10° HDT. A linear mixed-effects model was used to assess the effect of HDT on hemodynamic variables.

Results: The HDT was explored in seven POTS patients and an additional seven POTS patients without HDT served as controls. In the HDT arm, four POTS patients had overlapping diagnoses of myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) and one patient had comorbidity of post-acute sequelae of SARS-CoV-2 infection (PASC). HDT lowered heart rate by 10% and increased end-tidal CO2 by 8%. There was no change in other cardiovascular variables.

Conclusions: In the acute setting, HDT is safe. HDT reduces the heart rate presumably by modulating baroreflex by enhancing preload and stroke volume, which in turn increases thoracic blood volume with a net effect of parasympathetic cardiovagal activation and/or sympathetic withdrawal. This pilot study provides a foundation to proceed with longitudinal studies exploring the long-term effect of repetitive HDT in conditions associated with preload failure such as POTS, ME/CSF, and PASC.

Source: Novak P. Head-down tilt reduces the heart rate in postural tachycardia syndrome in acute setting: a pilot study. Neurol Sci. 2023 Nov 3. doi: 10.1007/s10072-023-07153-5. Epub ahead of print. PMID: 37919442. https://pubmed.ncbi.nlm.nih.gov/37919442/

Network autonomic analysis of post-acute sequelae of COVID-19 and postural tachycardia syndrome

Abstract:

Background: The autonomic nervous system (ANS) is a complex network where sympathetic and parasympathetic domains interact inside and outside of the network. Correlation-based network analysis (NA) is a novel approach enabling the quantification of these interactions. The aim of this study is to assess the applicability of NA to assess relationships between autonomic, sensory, respiratory, cerebrovascular, and inflammatory markers on post-acute sequela of COVID-19 (PASC) and postural tachycardia syndrome (POTS).

Methods: In this retrospective study, datasets from PASC (n = 15), POTS (n = 15), and matched controls (n = 11) were analyzed. Networks were constructed from surveys (autonomic and sensory), autonomic tests (deep breathing, Valsalva maneuver, tilt, and sudomotor test) results using heart rate, blood pressure, cerebral blood flow velocity (CBFv), capnography, skin biopsies for assessment of small fiber neuropathy (SFN), and various inflammatory markers. Networks were characterized by clusters and centrality metrics.

Results: Standard analysis showed widespread abnormalities including reduced orthostatic CBFv in 100%/88% (PASC/POTS), SFN 77%/88%, mild-to-moderate dysautonomia 100%/100%, hypocapnia 87%/100%, and elevated inflammatory markers. NA showed different signatures for both disorders with centrality metrics of vascular and inflammatory variables playing prominent roles in differentiating PASC from POTS.

Conclusions: NA is suitable for a relationship analysis between autonomic and nonautonomic components. Our preliminary analyses indicate that NA can expand the value of autonomic testing and provide new insight into the functioning of the ANS and related systems in complex disease processes such as PASC and POTS.

Source: Novak P, Giannetti MP, Weller E, Hamilton MJ, Mukerji SS, Alabsi HS, Systrom D, Marciano SP, Felsenstein D, Mullally WJ, Pilgrim DM, Castells M. Network autonomic analysis of post-acute sequelae of COVID-19 and postural tachycardia syndrome. Neurol Sci. 2022 Sep 28:1–12. doi: 10.1007/s10072-022-06423-y. Epub ahead of print. PMID: 36169757; PMCID: PMC9517969. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9517969/ (Full text)

Postural neurocognitive and neuronal activated cerebral blood flow deficits in young chronic fatigue syndrome patients with postural tachycardia syndrome

Abstract:

Neurocognition is impaired in chronic fatigue syndrome (CFS). We propose that the impairment relates to postural cerebral hemodynamics.

Twenty-five CFS subjects and twenty 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 value and every tilt angle using transcranial Doppler ultrasound.

N-back outcome in control subjects decreased with n valve but was independent of tilt angle. N-back outcome in CFS subjects decreased with n value but deteriorated as orthostasis progressed. Absolute mean CBFV was slightly less than in control subjects in CFS subject at each angle. Activated CBFV in control subjects was independent of tilt angle and increased with n value.

In contrast, activated CBFV averaged 0 in CFS subjects, decreased with angle, and was less than in control subjects. CCP was increased in CFS subjects, suggesting increased vasomotor tone and decreased metabolic control of CBFV. CCP did not change with orthostasis in CFS subjects 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 subjects. CBFV activation, normally tightly linked to cognitive neuronal activity, is unrelated to cognitive performance in CFS subjects; the increased CCP and vasomotor tone may indicate an uncoupling of the neurovascular unit during orthostasis.

 

Source: Stewart JM, Medow MS, Messer ZR, Baugham IL, Terilli C, Ocon AJ. Postural neurocognitive and neuronal activated cerebral blood flow deficits in young chronic fatigue syndrome patients with postural tachycardia syndrome. Am J Physiol Heart Circ Physiol. 2012 Mar 1;302(5):H1185-94. doi: 10.1152/ajpheart.00994.2011. Epub 2011 Dec 16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3311460/ (Full article)

 

Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome

Abstract:

CFS (chronic fatigue syndrome) is commonly co-morbid with POTS (postural tachycardia syndrome). Individuals with CFS/POTS experience unrelenting fatigue, tachycardia during orthostatic stress and ill-defined neurocognitive impairment, often described as ‘mental fog’. We hypothesized that orthostatic stress causes neurocognitive impairment in CFS/POTS related to decreased CBFV (cerebral blood flow velocity).

A total of 16 CFS/POTS and 20 control subjects underwent graded tilt table testing (at 0, 15, 30, 45, 60 and 75°) with continuous cardiovascular, cerebrovascular, and respiratory monitoring and neurocognitive testing using an n-back task at each angle. The n-back task tests working memory, concentration, attention and information processing. The n-back task imposes increasing cognitive challenge with escalating (0-, 1-, 2-, 3- and 4-back) difficulty levels. Subject dropout due to orthostatic presyncope at each angle was similar between groups.

There were no n-back accuracy or RT (reaction time) differences between groups while supine. CFS/POTS subjects responded less correctly during the n-back task test and had greater nRT (normalized RT) at 45, 60 and 75°. Furthermore, at 75° CFS/POTS subjects responded less correctly and had greater nRT than controls during the 2-, 3- and 4-back tests. Changes in CBFV were not different between the groups and were not associated with n-back task test scores.

Thus we conclude that increasing orthostatic stress combined with a cognitive challenge impairs the neurocognitive abilities of working memory, accuracy and information processing in CFS/POTS, but that this is not related to changes in CBFV. Individuals with CFS/POTS should be aware that orthostatic stress may impair their neurocognitive abilities.

 

Source: 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 Mar;122(5):227-38. doi: 10.1042/CS20110241. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368269/ (Full article)

 

Cerebral and systemic hemodynamics changes during upright tilt in chronic fatigue syndrome

Abstract:

BACKGROUND AND PURPOSE: During head-up tilt (HUT), patients with chronic fatigue syndrome (CFS) have higher rates of neurally mediated hypotension (NMH) and postural tachycardia syndrome (POTS) than healthy controls. The authors studied whether patients with CFS were also more likely to have abnormal cerebral blood flow velocity (CBFV) compared with controls in response to orthostatic stress.

METHODS: Transcranial Doppler monitoring of middle cerebral artery (MCA) CBFV was performed during 3-stage HUT prospectively in 26 patients with CFS and 23 healthy controls. At the same time, continuous monitoring of arterial blood pressure (BP), heart rate (HR), endtidal CO2 (ET-CO2) were performed. Results are reported as mean +/- SD.

RESULTS: NMH developed in 21 patients with CFS and in 14 controls (P = .22). POTS was present in 9 CFS patients and 7 controls (P = .76). Supine HR was higher in CFS patients, but all other hemodynamics and CBFV measures were similar at baseline. The median time to hypotension did not differ, but the median time to onset of orthostatic symptoms was shorter in those with CFS (P < .001). The CBFV did not differ between groups in the supine posture, at 1 or 5 minutes after upright tilt, at 5 or 1 minute before the end of the test, or at termination of the test. Mean CBFV fell at termination of tilt testing in those with CFS and controls. ET-CO2 was lower at termination of the test in those with CFS versus controls (P = .002).

CONCLUSIONS: The results of this study are not consistent with the hypothesis that patients with CFS have a distinctive pattern of MCA CBFV changes in response to orthostatic stress.

 

Source: Razumovsky AY, DeBusk K, Calkins H, Snader S, Lucas KE, Vyas P, Hanley DF, Rowe PC. Cerebral and systemic hemodynamics changes during upright tilt in chronic fatigue syndrome. J Neuroimaging. 2003 Jan;13(1):57-67. http://www.ncbi.nlm.nih.gov/pubmed/12593133