Category: Symptoms

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)

Post-exertional Symptoms Distinguish Myalgic encephalomyelitis/chronic Fatigue Syndrome Subjects From Healthy Controls

Abstract:

Background: Post-exertional malaise (PEM) is an exacerbation of symptoms that leads to a reduction in functionality. Recognition of PEM is important for the diagnosis and treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Objective: Symptoms following cardiopulmonary exercise testing were compared between ME/CFS patients and healthy controls.

Methods: Open-ended questionnaires were provided to subjects following two maximal exercise tests, 24 hours apart. Subjects evaluated how they felt at five time points. Responses were classified into 19 symptom categories.

Results: ME/CFS subjects (n = 49) reported an average of 14±7 symptoms compared to 4±3 by controls (n = 10). During the seven days afterwards, ME/CFS subjects reported 4±3 symptoms. None were reported by controls. Fatigue, cognitive dysfunction, and sleep problems were reported with the greatest frequency. ME/CFS patients reported more symptom categories at higher frequencies than controls. The largest differences were observed in cognitive dysfunction, decrease in function, and positive feelings.

Conclusions: A standardized exertional stimulus produced prolonged, diverse symptoms in ME/CFS subjects. This provides clues to the underlying pathophysiology of ME/CFS, leading to improved diagnosis and treatment.

Source: Mateo LJ, Chu L, Stevens S, et al. Post-exertional symptoms distinguish myalgic encephalomyelitis/chronic fatigue syndrome subjects from healthy controls [published online ahead of print, 2020 Jun 16]. Work. 2020;10.3233/WOR-203168. doi:10.3233/WOR-203168 https://pubmed.ncbi.nlm.nih.gov/32568143/

Clinically Accessible Tools for Documenting the Impact of Orthostatic Intolerance on Symptoms and Function in ME/CFS

Abstract:

Background: Clinical observations have indicated that hours of upright activity (HUA) reported by Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients correlated with orthostatic symptoms and impaired physical function. This study examined the relationship between HUA and orthostatic intolerance (OI).

Methods: Twenty-five female ME/CFS subjects and 25 age and race matched female healthy controls (HCs) were enrolled. Subjects reported HUA (defined as hours per day spent with feet on the floor) and completed questionnaires to assess the impact of OI on daily activities and symptoms. ME/CFS patients were categorized into those with <5 HUA and ≥5 HUA and analyzed by employment status. Data analysis used one-way ANOVA.

Results: ME/CFS patients had fewer HUA, worse symptoms and greater interference with daily activities due to OI than HCs. The <5 HUA ME/CFS subjects had more severe OI related symptoms than ≥5 HUA ME/CFS subjects even though OI interfered with daily activities similarly. Only 33% of ME/CFS subjects were employed and all were ≥5 HUA ME/CFS subjects with an average HUA of 8.

Conclusions: ME/CFS subjects experienced more frequent and severe OI symptoms, higher interference with daily activities, and reduced ability to work than HCs. Reported HUA and assessment of OI using standardized instruments may be useful clinical tools for physicians in the diagnosis, treatment and management of ME/CFS patients.

Source: Lee J, Wall P, Kimler C, Bateman L, Vernon SD. Clinically accessible tools for documenting the impact of orthostatic intolerance on symptoms and function in ME/CFS [published online ahead of print, 2020 Jun 16]. Work. 2020;10.3233/WOR-203169. doi:10.3233/WOR-203169 https://pubmed.ncbi.nlm.nih.gov/32568144/

Epidemiological and Clinical Factors Associated With Post-Exertional Malaise Severity in Patients With Myalgic encephalomyelitis/chronic Fatigue Syndrome

Abstract:

Background: Post-exertional malaise (PEM), the cardinal feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), occurs generally after exposure to a stressor. It is characterized by the worsening of ME/CFS symptoms and results in aggravating the course of the disease and the quality of life of patients. Due to its unpredictable onset, severity, and recovery time, identifying patients with higher risk for severe PEM would allow preventing or reducing its occurrence. We thus aimed at defining possible factors that could be associated with PEM severity.

Methods: Adult patients fulfilling ME international consensus criteria who attended the internal medicine department of University hospital Angers-France between October 2011 and December 2019 were included retrospectively. All patients were systematically hospitalized for an etiological workup and overall assessment. We reviewed their medical records for data related to the assessment: epidemiological data, fatigue features, clinical manifestations, and ME/CFS precipitants. PEM severity was appreciated by the Center for Disease Control self-reported questionnaire. The study population was classified into quartiles according to PEM severity scores. Analyses were performed with ordinal logistic regression to compare quartile groups.

Results: 197 patients were included. PEM severity was found to be positively associated with age at disease onset ≥ 32 years (OR 1.8 [95% CI 1.1-3.0] (p = 0.03)), recurrent infections during the course of the disease (OR 2.1 [95% CI 1.2-3.7] (p = 0.009)), and when ME/CFS was elicited by a gastrointestinal infectious precipitant (OR 5.7 [1.7-19.3] (p = 0.006)).

Conclusion: We identified some epidemiological and clinical features, which were positively associated with PEM severity in subsets of ME/CFS patients. This could help improving disease management and patients’ quality of life.

Source: Ghali A, Richa P, Lacout C, et al. Epidemiological and clinical factors associated with post-exertional malaise severity in patients with myalgic encephalomyelitis/chronic fatigue syndrome. J Transl Med. 2020;18(1):246. Published 2020 Jun 22. doi:10.1186/s12967-020-02419-4 https://pubmed.ncbi.nlm.nih.gov/32571354/

Chronic Pain Syndromes and Their Laryngeal Manifestations

Abstract:

IMPORTANCE: Fibromyalgia syndrome (FMS), irritable bowel syndrome (IBS), and chronic fatigue syndrome (CFS) are traditionally considered as distinct entities grouped under chronic pain syndrome (CPS) of an unknown origin. However, these 3 disorders may exist on a spectrum with a shared pathophysiology.

OBJECTIVE: To investigate whether the clinical presentation of FMS, IBS, and CFS is similar in a population presenting with voice and laryngeal disorders.

DESIGN, SETTING, AND PARTICIPANTS: This case series was a retrospective review of the medical records and clinical notes of patients treated between January 1, 2016, and December 31, 2017, at the Johns Hopkins Voice Center in Baltimore, Maryland. Patients with at least 1 CPS of interest (FMS, IBS, or CFS) were included (n = 215), along with patients without such diagnoses (n = 4034). Diagnoses, demographic, and comorbidity data were reviewed. Diagnoses related to voice and laryngeal disorders were subdivided into 5 main categories (laryngeal pathology, functional voice disorders, airway problems, swallowing problems, and other diagnoses).

MAIN OUTCOMES AND MEASURES: Prevalence and odds ratios of 45 voice and laryngeal disorders were reviewed. Odds ratios (ORs) were calculated by comparing patients with CPS with control patients.

RESULTS: In total, 4249 individuals were identified; 215 (5.1%) had at least 1 CPS and 4034 (94.9%) were control participants. Patients with CPS were 3 times more likely to be women compared with the control group (173 of 215 [80.5%] vs 2318 of 4034 [57.5%]; OR, 3.156; 95% CI, 2.392-4.296), and the CPS group had a mean (SD) age of 57.80 (15.30) years compared with the mean (SD) age of 55.77 (16.97) years for the control group. Patients with CPS were more likely to present with functional voice disorders (OR, 1.812; 95% CI, 1.396-2.353) and less likely to present with laryngeal pathology (OR, 0.774; 95% CI, 0.610-0.982) or airway problems (OR, 0.474; 95% CI, 0.285-0.789).

CONCLUSIONS AND RELEVANCE: The voice and airway presentation of patients with FMS, IBS, and/or CFS appears to be indistinguishable from each other. This finding suggests that these 3 diseases share upper airway symptoms.

Source: Piersiala K, Akst LM, Hillel AT, Best SR. Chronic Pain Syndromes and Their Laryngeal Manifestations. JAMA Otolaryngol Head Neck Surg. 2020 Apr 30. doi: 10.1001/jamaoto.2020.0530. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32352483

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)

Parasympathetic activity is reduced during slow-wave sleep, but not resting wakefulness, in patients with chronic fatigue syndrome

Abstract:

STUDY OBJECTIVES: Physiological dearousal characterized by an increase in parasympathetic nervous system activity is important for good-quality sleep. Previous research shows that nocturnal parasympathetic activity (reflected by heart rate variability [HRV]) is diminished in individuals with chronic fatigue syndrome (CFS), suggesting hypervigilant sleep. This study investigated differences in nocturnal autonomic activity across sleep stages and explored the association of parasympathetic activity with sleep quality and self-reported physical and psychological wellbeing in individuals with CFS.

METHODS: Twenty-four patients with medically diagnosed CFS, and 24 matched healthy control individuals participated. Electroencephalography and HRV were recorded during sleep in participants’ homes using a minimally invasive ambulatory device. Questionnaires were used to measure self-reported wellbeing and sleep quality.

RESULTS: Sleep architecture in patients with CFS differed from that of control participants in slower sleep onset, more awakenings, and a larger proportion of time spent in slow-wave sleep (SWS). Linear mixed-model analyses controlling for age revealed that HRV reflecting parasympathetic activity (normalized high frequency power) was reduced in patients with CFS compared to control participants, particularly during deeper stages of sleep. Poorer self-reported wellbeing and sleep quality was associated with reduced parasympathetic signaling during deeper sleep, but not during wake before sleep, rapid eye movement sleep, or with the proportion of time spent in SWS.

CONCLUSIONS: Autonomic hypervigilance during the deeper, recuperative stages of sleep is associated with poor quality sleep and self-reported wellbeing. Causal links need to be confirmed but provide potential intervention opportunities for the core symptom of unrefreshing sleep in CFS.

© 2020 American Academy of Sleep Medicine.

Source: Fatt SJ, Beilharz JE, Joubert M, Wilson C, Lloyd AR, Vollmer-Conna U, Cvejic E. Parasympathetic activity is reduced during slow-wave sleep, but not resting wakefulness, in patients with chronic fatigue syndrome. J Clin Sleep Med. 2020 Jan 15;16(1):19-28. doi: 10.5664/jcsm.8114. Epub 2019 Nov 27. https://www.ncbi.nlm.nih.gov/pubmed/31957647

Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome

Abstract:

Elevated blood lactate after moderate exercise was reported in some of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We hypothesised that blood lactate could be also elevated in resting conditions. We aimed investigating the frequency of elevated lactate at rest in ME/CFS patients, and comparing characteristics of ME/CFS patients with and without elevated lactate.

Patients fulfilling international consensus criteria for ME/CFS who attended the internal medicine department of University hospital Angers-France between October 2011 and December 2017 were included retrospectively. All patients were systematically hospitalised for an aetiological workup and overall assessment.

We reviewed their medical records for data related to the assessment: clinical characteristics, comorbidities, fatigue features, post-exertional malaise (PEM) severity, and results of 8 lactate measurements at rest. Patients having ≥1 lactate measurement ≥2 mmol/L defined elevated lactate group. The study included 123 patients. Elevated (n = 55; 44.7%) and normal (n = 68; 55.3%) lactate groups were comparable except for PEM, which was more severe in the elevated lactate group after adjusting for age at disease onset, sex, and comorbidities (OR 2.47, 95% CI: 1.10-5.55). ME/CFS patients with elevated blood lactate at rest may be at higher risk for more severe PEM. This finding may be of interest in ME/CFS management.

Source: Ghali A, Lacout C, Ghali M, Gury A, Beucher AB, Lozac’h P, Lavigne C, Urbanski G. Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome. Sci Rep. 2019 Dec 11;9(1):18817. doi: 10.1038/s41598-019-55473-4. ncbi.nlm.nih.gov/pubmed/31827223

Parasympathetic activity is reduced during slow-wave sleep, but not resting wakefulness, in patients with chronic fatigue syndrome

Abstract:

STUDY OBJECTIVES: Physiological dearousal characterized by an increase in parasympathetic nervous system activity is important for good-quality sleep. Previous research shows that nocturnal parasympathetic activity (reflected by heart rate variability [HRV]) is diminished in individuals with chronic fatigue syndrome (CFS), suggesting hypervigilant sleep. This study investigated differences in nocturnal autonomic activity across sleep stages and explored the association of parasympathetic activity with sleep quality and self-reported physical and psychological wellbeing in individuals with CFS.

METHODS: Twenty-four patients with medically diagnosed CFS, and 24 matched healthy control individuals participated. Electroencephalography and HRV were recorded during sleep in participants’ homes using a minimally invasive ambulatory device. Questionnaires were used to measure self-reported wellbeing and sleep quality.

RESULTS: Sleep architecture in patients with CFS differed from that of control participants in slower sleep onset, more awakenings, and a larger proportion of time spent in slow-wave sleep (SWS). Linear mixed-model analyses controlling for age revealed that HRV reflecting parasympathetic activity (normalized high frequency power) was reduced in patients with CFS compared to control participants, particularly during deeper stages of sleep. Poorer self-reported wellbeing and sleep quality was associated with reduced parasympathetic signaling during deeper sleep, but not during wake before sleep, rapid eye movement sleep, or with the proportion of time spent in SWS.

CONCLUSIONS: Autonomic hypervigilance during the deeper, recuperative stages of sleep is associated with poor quality sleep and self-reported wellbeing. Causal links need to be confirmed but provide potential intervention opportunities for the core symptom of unrefreshing sleep in CFS.

© 2019 American Academy of Sleep Medicine.

Source: Fatt SJ, Beilharz JE, Joubert M, Wilson C, Lloyd AR, Vollmer-Conna U, Cvejic E. Parasympathetic activity is reduced during slow-wave sleep, but not resting wakefulness, in patients with chronic fatigue syndrome. J Clin Sleep Med. 2019 Nov 27. pii: jc-19-00271. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31771749

Psychometric properties of the PROMIS® Fatigue Short Form 7a among adults with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

PURPOSE: To evaluate the psychometric properties of the Patient-Reported Outcome Measurement Information System® Fatigue Short Form 7a (PROMIS F-SF) among people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

METHODS: Analyses were conducted using data from the Multi-Site Clinical Assessment of ME/CFS study, which recruited participants from seven ME/CFS specialty clinics across the US. Baseline and follow-up data from ME/CFS participants and healthy controls were used. Ceiling/Floor effects, internal consistency reliability, differential item functioning (DIF), known-groups validity, and responsiveness were examined.

RESULTS: The final sample comprised 549 ME/CFS participants at baseline, 386 of whom also had follow-up. At baseline, the sample mean of PROMIS F-SF T-score was 68.6 (US general population mean T-score of 50 and standard deviation of 10). The PROMIS F-SF demonstrated good internal consistency reliability (Cronbach’s α = 0.84) and minimal floor/ceiling effects. No DIF was detected by age or sex for any item. This instrument also showed good known-groups validity with medium-to-large effect sizes (η2 = 0.08-0.69), with a monotonic increase of the fatigue T-score across ME/CFS participant groups with low, medium, and high functional impairment as measured by three different variables (p < 0.01), and with significantly higher fatigue T-scores among ME/CFS participants than healthy controls (p < 0.0001). Acceptable responsiveness was found with small-to-medium effect sizes (Guyatt’s Responsiveness Statistic = 0.28-0.54).

CONCLUSIONS: Study findings support the reliability and validity of PROMIS F-SF as a measure of fatigue for ME/CFS and lend support to the drug development tool submission for qualifying this measure to evaluate therapeutic effect in ME/CFS clinical trials.

Source: Yang M, Keller S, Lin JS. Psychometric properties of the PROMIS® Fatigue Short Form 7a among adults with myalgic encephalomyelitis/chronic fatigue syndrome. Qual Life Res. 2019 Sep 10. doi: 10.1007/s11136-019-02289-4. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31506915