Tag: cerebral blood flow

Cerebral Blood Flow Is Reduced in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients During Mild Orthostatic Stress Testing: An Exploratory Study at 20 Degrees of Head-Up Tilt Testing

Abstract:

Introduction: In a study of 429 adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), we demonstrated that 86% had symptoms of orthostatic intolerance in daily life. Using extracranial Doppler measurements of the internal carotid and vertebral arteries during a 30-min head-up tilt to 70 degrees, 90% had an abnormal reduction in cerebral blood flow (CBF). A standard head-up tilt test of this duration might not be tolerated by the most severely affected bed-ridden ME/CFS patients. This study examined whether a shorter 15-min test at a lower 20 degree tilt angle would be sufficient to provoke reductions in cerebral blood flow in severe ME/CFS patients.

Methods and results: Nineteen severe ME/CFS patients with orthostatic intolerance complaints in daily life were studied: 18 females. The mean (SD) age was 35(14) years, body surface area (BSA) was 1.8(0.2) m2 and BMI was 24.0(5.4) kg/m2. The median disease duration was 14 (IQR 5-18) years. Heart rate increased, and stroke volume index and end-tidal CO2 decreased significantly during the test (p ranging from <0.001 to <0.0001). The cardiac index decreased by 26(7)%: p < 0.0001. CBF decreased from 617(72) to 452(63) mL/min, a 27(5)% decline. All 19 severely affected ME/CFS patients met the criteria for an abnormal CBF reduction.

Conclusions: Using a less demanding 20 degree tilt test for 15 min in severe ME/CFS patients resulted in a mean CBF decline of 27%. This is comparable to the mean 26% decline previously noted in less severely affected patients studied during a 30-min 70 degree head-up tilt. These observations have implications for the evaluation and treatment of severely affected individuals with ME/CFS.

Source: van Campen CLMC, Rowe PC, Visser FC. Cerebral Blood Flow Is Reduced in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients During Mild Orthostatic Stress Testing: An Exploratory Study at 20 Degrees of Head-Up Tilt Testing. Healthcare (Basel). 2020;8(2):E169. Published 2020 Jun 13. doi:10.3390/healthcare8020169 https://www.mdpi.com/2227-9032/8/2/169 (Full text)

A systematic review of neurological impairments in myalgic encephalomyelitis/ chronic fatigue syndrome using neuroimaging techniques

Abstract:

BACKGROUND: Myalgic encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a multi-system illness characterised by a diverse range of debilitating symptoms including autonomic and cognitive dysfunction. The pathomechanism remains elusive, however, neurological and cognitive aberrations are consistently described. This systematic review is the first to collect and appraise the literature related to the structural and functional neurological changes in ME/CFS patients as measured by neuroimaging techniques and to investigate how these changes may influence onset, symptom presentation and severity of the illness.

METHODS: A systematic search of databases Pubmed, Embase, MEDLINE (via EBSCOhost) and Web of Science (via Clarivate Analytics) was performed for articles dating between December 1994 and August 2019. Included publications report on neurological differences in ME/CFS patients compared with healthy controls identified using neuroimaging techniques such as magnetic resonance imaging, positron emission tomography and electroencephalography. Article selection was further refined based on specific inclusion and exclusion criteria. A quality assessment of included publications was completed using the Joanna Briggs Institute checklist.

RESULTS: A total of 55 studies were included in this review. All papers assessed neurological or cognitive differences in adult ME/CFS patients compared with healthy controls using neuroimaging techniques. The outcomes from the articles include changes in gray and white matter volumes, cerebral blood flow, brain structure, sleep, EEG activity, functional connectivity and cognitive function. Secondary measures including symptom severity were also reported in most studies.

CONCLUSIONS: The results suggest widespread disruption of the autonomic nervous system network including morphological changes, white matter abnormalities and aberrations in functional connectivity. However, these findings are not consistent across studies and the origins of these anomalies remain unknown. Future studies are required confirm the potential neurological contribution to the pathology of ME/CFS.

Source: Maksoud R, du Preez S, Eaton-Fitch N, Thapaliya K, Barnden L, Cabanas H, Staines D, Marshall-Gradisnik S. A systematic review of neurological impairments in myalgic encephalomyelitis/ chronic fatigue syndrome using neuroimaging techniques. PLoS One. 2020 Apr 30;15(4):e0232475. doi: 10.1371/journal.pone.0232475. eCollection 2020. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232475

Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia: a quantitative, controlled study using Doppler echography

Abstract:

Objective: The underlying hypothesis in orthostatic intolerance (OI) syndromes is that symptoms are associated with cerebral blood flow (CBF) reduction. Indirect CBF measurements (transcranial Doppler flow velocities), provide inconsistent support of this hypothesis. The aim of the study was to measure CBF during a 30 min head-up tilt test (HUT), using Doppler flow imaging of carotid and vertebral arteries, in individuals with chronic fatigue syndrome/myalgic encephalomyelitis (ME/CFS), a condition with a high prevalence of OI.

Methods: 429 ME/CFS patients were studied: 247 had a normal heart rate (HR) and blood pressure (BP) response to HUT, 62 had delayed orthostatic hypotension (dOH), and 120 had postural orthostatic tachycardia syndrome (POTS). We also studied 44 healthy controls (HC). CBF measurements were made at mid-tilt and end-tilt. Before mid-tilt, we administered a verbal questionnaire to ascertain for 15 OI symptoms.

Results: End-tilt CBF reduction was 7% in HC versus 26% in the overall ME/CFS group, 24% in patients with a normal HR/BP response, 28% in those with dOH, and 29% in POTS patients (all P<.0005). Using a lower limit of normal of 2SD of CBF reduction in HC (13% reduction), 82% of patients with normal HR/BP response, 98% with dOH and 100% with POTS showed an abnormal CBF reduction. There was a linear correlation of summed OI symptoms with the degree of CBF reduction at mid-tilt (P<.0005).

Conclusions: During HUT, extracranial Doppler measurements demonstrate that CBF is reduced in ME/CFS patients with POTS, dOH, and even in those without HR/BP abnormalities.

Significance: This study shows that orthostatic intolerance symptoms are related to CBF reduction, and that the majority of ME/CFS patients (90%) show an abnormal cerebral flow reduction during orthostatic stress testing. This may have implications for the diagnosis and treatment of ME/CFS patients.

Source: C. (Linda) M.C.van Campen, Freek W.A. Verheugt, Peter C. Rowe, Frans C.Visser. Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia: a quantitative, controlled study using Doppler echography. Clinical Neurophysiology Practice. Available online 8 February 2020. https://doi.org/10.1016/j.cnp.2020.01.003 https://www.sciencedirect.com/science/article/pii/S2467981X20300044 (Full text)

Cerebral blood flow and heart rate variability predict fatigue severity in patients with chronic fatigue syndrome

Abstract:

Prolonged, disabling fatigue is the hallmark of chronic fatigue syndrome (CFS). Previous neuroimaging studies have provided evidence for nervous system involvement in CFS etiology, including perturbations in brain structure/function. In this arterial spin labeling (ASL) MRI study, we examined variability in cerebral blood flow (CBFV) and heart rate (HRV) in 28 women: 14 with CFS and 14 healthy controls. We hypothesized that CBFV would be reduced in individuals with CFS compared to healthy controls, and that increased CBFV and HRV would be associated with lower levels of fatigue in affected individuals.

Our results provided support for these hypotheses. Although no group differences in CBFV or HRV were detected, greater CBFV and more HRV power were both associated with lower fatigue symptom severity in individuals with CFS. Exploratory statistical analyses suggested that protective effects of high CBFV were greatest in individuals with low HRV. We also found novel evidence of bidirectional association between the very high frequency (VHF) band of HRV and CBFV. Taken together, the results of this study suggest that CBFV and HRV are potentially important measures of adaptive capacity in chronic illnesses like CFS. Future studies should address these measures as potential therapeutic targets to improve outcomes and reduce symptom severity in individuals with CFS.

Source: Boissoneault J, Letzen J, Robinson M, Staud R. Cerebral blood flow and heart rate variability predict fatigue severity in patients with chronic fatigue syndrome. Brain Imaging Behav. 2018 May 31. doi: 10.1007/s11682-018-9897-x. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29855991

Task Related Cerebral Blood Flow Changes of Patients with Chronic Fatigue Syndrome: An Arterial Spin Labeling Study.

Abstract:

PURPOSE: One hallmark of chronic fatigue syndrome (ME/CFS) is task related worsening of fatigue. Global brain hypoperfusion, abnormal regional activation, and altered functional connectivity of brain areas associated with cognition and memory have been reported but remain controversial.

METHODS: We enrolled 17 female participants fulfilling the CDC Criteria for ME/CFS and 16 matched healthy controls (HC). Using a 3T-Phillips Achieva MRI-scanner, pseudo-continuous arterial spin-labeling (pCASL), was used to study the dynamics of regional cerebral blood flow (rCBF) and their relationship to mental fatigue in ME/CFS patients and HC during a demanding cognitive task, i.e. modified Paced-Auditory-Serial-Addition-Testing (PASAT).

RESULTS: ME/CFS subjects reported more fatigue than HC at baseline (p < .01). Global brain perfusion of ME/CFS and HC subjects was similar at rest. The PASAT resulted in significantly increased fatigue in ME/CFS participants and HC. Although not different between groups, overall CBF significantly increased over the first 3 min of the PASAT and then decreased thereafter. Regional CBF (rCBF) changes were significantly different between groups during the post-task recovery period. Whereas improvement of fatigue of ME/CFS subjects was associated with decreased rCBF in both superior temporal gyri (STG), precuneus, and fusiform gyrus, it was associated with increased rCBF in the same areas in HC.

CONCLUSIONS: Our results suggest that ME/CFS is associated with normal global CBF at rest and during a strenuous task (PASAT); however rCBF of several brain regions associated with memory, goal-oriented attention, and visual function was differentially associated with recovery from fatigue in ME/CFS patients and HC.

Source: Staud R, Boissoneault J, Craggs JG, Lai S, Robinson ME. Task Related Cerebral Blood Flow Changes of Patients with Chronic Fatigue Syndrome: An Arterial Spin Labeling Study. Fatigue. 2018;6(2):63-79. doi: 10.1080/21641846.2018.1453919. Epub 2018 Mar 20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914525/  (Full study)

Task related cerebral blood flow changes of patients with chronic fatigue syndrome: an arterial spin labeling study

Abstract:

Purpose: One hallmark of chronic fatigue syndrome (ME/CFS) is task related worsening of fatigue. Global brain hypoperfusion, abnormal regional activation, and altered functional connectivity of brain areas associated with cognition and memory have been reported but remain controversial.

Methods: We enrolled 17 female participants fulfilling the CDC Criteria for ME/CFS and 16 matched healthy controls (HC). Using a 3T-Phillips Achieva MRI-scanner, pseudo-continuous arterial spin-labeling (pCASL), was used to study the dynamics of regional cerebral blood flow (rCBF) and their relationship to mental fatigue in ME/CFS patients and HC during a demanding cognitive task, i.e. modified Paced-Auditory-Serial-Addition-Testing (PASAT).

Results: ME/CFS subjects reported more fatigue than HC at baseline (p < .01). Global brain perfusion of ME/CFS and HC subjects was similar at rest. The PASAT resulted in significantly increased fatigue in ME/CFS participants and HC. Although not different between groups, overall CBF significantly increased over the first 3 min of the PASAT and then decreased thereafter. Regional CBF (rCBF) changes were significantly different between groups during the post-task recovery period. Whereas improvement of fatigue of ME/CFS subjects was associated with decreased rCBF in both superior temporal gyri (STG), precuneus, and fusiform gyrus, it was associated with increased rCBF in the same areas in HC.

Conclusions: Our results suggest that ME/CFS is associated with normal global CBF at rest and during a strenuous task (PASAT); however rCBF of several brain regions associated with memory, goal-oriented attention, and visual function was differentially associated with recovery from fatigue in ME/CFS patients and HC.

Source: Roland Staud, Jeff Boissoneault, Jason G. Craggs, Song Lai & Michael E. Robinson (2018) Task related cerebral blood flow changes of patients with chronic fatigue syndrome: an arterial spin labeling study, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2018.1453919

Efficacy and safety of noophen in the treatment of chronic fatigue syndrome in patients with cerebrovascular insufficiency

Abstract:

AIM: To assess the efficacy and safety of noophen in the treatment of chronic fatigue syndrome in patients with cerebrovascular insufficiency.

MATERIAL AND METHODS: Fifty-three patients with cerebrovascular disease, who complain about persistent fatigue, were randomized into two groups. Patients of the main group (n=33) received standard therapy and noophen, patients of the control group (n=20) received only standard therapy. Treatment efficacy was assessed using MFI-20, HADS-A, LSEQ. In addition, cognitive functioning was evaluated using Schulte test.

RESULTS AND CONCLUSION: Treatment with noophen resulted in the marked decrease in the total intensity of fatigue measured with MFI-20. The decrease in fatigue intensity by 30-50% was observed in 3/4 of patients of the main group. Noophen reduced all components of fatigue syndrome, including a mental component, and improved motivation. The reduction of the mental fatigue component was combined with the improvement of cognitive functioning assessed with Schulte test. Therefore, the effect of noophen on motivation and mental fatigue component can promote cognitive training in patients with cerebrovascular insufficiency.

Source: Vorob’eva OV, Rusaya VV. Efficacy and safety of noophen in the treatment of chronic fatigue syndrome in patients with cerebrovascular insufficiency. [Article in Russian; Abstract available in Russian from the publisher] Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(11):31-36. doi: 10.17116/jnevro201711711131-36. https://www.ncbi.nlm.nih.gov/pubmed/29265084

Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses

Abstract:

Although altered resting-state functional connectivity (FC) is a characteristic of many chronic pain conditions, it has not yet been evaluated in patients with chronic fatigue. Our objective was to investigate the association between fatigue and altered resting-state FC in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Thirty-six female subjects, 19 ME/CFS and 17 healthy controls, completed a fatigue inventory before undergoing functional magnetic resonance imaging. Two methods, (1) data driven and (2) model based, were used to estimate and compare the intraregional FC between both groups during the resting state (RS).

The first approach using independent component analysis was applied to investigate five RS networks: the default mode network, salience network (SN), left frontoparietal networks (LFPN) and right frontoparietal networks, and the sensory motor network (SMN).

The second approach used a priori selected seed regions demonstrating abnormal regional cerebral blood flow (rCBF) in ME/CFS patients at rest. In ME/CFS patients, Method-1 identified decreased intrinsic connectivity among regions within the LFPN. Furthermore, the FC of the left anterior midcingulate with the SMN and the connectivity of the left posterior cingulate cortex with the SN were significantly decreased.

For Method-2, five distinct clusters within the right parahippocampus and occipital lobes, demonstrating significant rCBF reductions in ME/CFS patients, were used as seeds. The parahippocampal seed and three occipital lobe seeds showed altered FC with other brain regions. The degree of abnormal connectivity correlated with the level of self-reported fatigue.

Our results confirm altered RS FC in patients with ME/CFS, which was significantly correlated with the severity of their chronic fatigue.

 

Source: Gay CW, Robinson ME, Lai S, O’Shea A, Craggs JG, Price DD, Staud R. Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses. Brain Connect. 2016 Feb;6(1):48-56. doi: 10.1089/brain.2015.0366. Epub 2015 Nov 10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744887/ (Full article)

 

Cerebral vascular control is associated with skeletal muscle pH in chronic fatigue syndrome patients both at rest and during dynamic stimulation

Abstract:

Cerebral blood flow (CBF) is maintained despite changing systemic blood pressure through cerebral vascular control, with such tight regulation believed to be under local tissue control. Chronic fatigue syndrome (CFS) associates with a wide range of symptoms, including orthostatic intolerance, skeletal muscle pH abnormalities and cognitive impairment.

CFS patients are known to have reduced CBF and orthostatic intolerance associates with abnormal vascular regulation, while skeletal muscle pH abnormalities associate with autonomic dysfunction. These findings point to autonomic dysfunction as the central feature of CFS, and cerebral vascular control being influenced by factors outside of the brain, a macroscopic force affecting the stability of regional regulation. We therefore explored whether there was a physiological link between cerebral vascular control and skeletal muscle pH management in CFS. Seventeen consecutive CFS patients fulfilling the Fukuda criteria were recruited from our local CFS clinical service. To probe the static scenario, CBF and skeletal muscle pH were measured at rest using MRI and (31)P magnetic resonance spectroscopy ((31)P-MRS). To examine dynamic control, brain functional MRI was performed concurrently with Valsalva manoeuvre (VM), a standard autonomic function challenge, while (31)P-MRS was performed during plantar flexion exercise.

Significant inverse correlation was seen between CBF and skeletal muscle pH at rest (r = – 0.67, p < 0.01). Prolonged cerebral vascular constriction during the sympathetic phase of VM was associated with higher pH in skeletal muscle after plantar flexion exercise (r = 0.69, p < 0.008). In conclusion, cerebral vascular control is closely related to skeletal muscle pH both at rest and after dynamic stimulation in CFS.

 

Source: He J, Hollingsworth KG, Newton JL, Blamire AM. Cerebral vascular control is associated with skeletal muscle pH in chronic fatigue syndrome patients both at rest and during dynamic stimulation. Neuroimage Clin. 2013 Jan 5;2:168-73. doi: 10.1016/j.nicl.2012.12.006. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777833/ (Full article)

 

Caught in the thickness of brain fog: exploring the cognitive symptoms of Chronic Fatigue Syndrome

Abstract:

Chronic Fatigue Syndrome (CFS) is defined as greater than 6 months of persistent fatigue that is experienced physically and cognitively. The cognitive symptoms are generally thought to be a mild cognitive impairment, but individuals with CFS subjectively describe them as “brain fog.” The impairment is not fully understood and often is described as slow thinking, difficulty focusing, confusion, lack of concentration, forgetfulness, or a haziness in thought processes.

Causes of “brain fog” and mild cognitive impairment have been investigated. Possible physiological correlates may be due to the effects of chronic orthostatic intolerance (OI) in the form of the Postural Tachycardia Syndrome (POTS) and decreases in cerebral blood flow (CBF). In addition, fMRI studies suggest that individuals with CFS may require increased cortical and subcortical brain activation to complete difficult mental tasks.

Furthermore, neurocognitive testing in CFS has demonstrated deficits in speed and efficiency of information processing, attention, concentration, and working memory. The cognitive impairments are then perceived as an exaggerated mental fatigue. As a whole, this is experienced by those with CFS as “brain fog” and may be viewed as the interaction of physiological, cognitive, and perceptual factors.

Thus, the cognitive symptoms of CFS may be due to altered CBF activation and regulation that are exacerbated by a stressor, such as orthostasis or a difficult mental task, resulting in the decreased ability to readily process information, which is then perceived as fatiguing and experienced as “brain fog.” Future research looks to further explore these interactions, how they produce cognitive impairments, and explain the perception of “brain fog” from a mechanistic standpoint.

 

Source: Ocon AJ. Caught in the thickness of brain fog: exploring the cognitive symptoms of Chronic Fatigue Syndrome. Front Physiol. 2013 Apr 5;4:63. doi: 10.3389/fphys.2013.00063. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617392/ (Full article)