Category: Symptoms

Numeric Rating Scales Show Prolonged Post-exertional Symptoms After Orthostatic Testing of Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Introduction: Muscle pain, fatigue, and concentration problems are common among individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These symptoms are commonly increased as part of the phenomenon of postexertional malaise (PEM). An increase in the severity of these symptoms is described following physical or mental exercise in ME/CFS patients. Another important symptom of ME/CFS is orthostatic intolerance, which can be detected by head-up tilt testing (HUT). The effect of HUT on PEM has not been studied extensively. For this purpose, we assessed numeric rating scales (NRS) for pain, fatigue, and concentration pre- and post-HUT. As pain is a core symptom in fibromyalgia (FM), we subgrouped ME/CFS patients by the presence or absence of FM.

Methods and Results: In eligible ME/CFS patients who underwent HUT, NRS of pain, fatigue, and concentration were obtained pre-HUT, immediately after HUT, at 24 and 48 h, and at 7 days posttest. We studied 174 ME/CFS patients with FM, 104 without FM, and 30 healthy controls (HC). Values for all symptoms were unchanged for HC pre- and post-HUT. Compared with pre-HUT, the three NRS post-HUT were significantly elevated in both ME/CFS patient groups even after 7 days. NRS pain was significantly higher at all time points measured in the ME/CFS patients with FM compared with those without FM. In ME/CFS patients, the maximum fatigue and concentration scores occurred directly post-HUT, whereas pain perception reached the maximum 24 h post-HUT.

Conclusion: NRS scores of pain, fatigue, and concentration were significantly increased even at 7 days post-HUT compared with pre-HUT in ME/CFS patients with and without FM, suggesting that orthostatic stress is an important determinant of PEM.

Source: C (Linda) M. C. van Campen, Peter C. Rowe, Freek W. A. Verheugt and Frans C. Visser. Numeric Rating Scales Show Prolonged Post-exertional Symptoms After Orthostatic Testing of Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front. Med., 27 January 2021 | https://doi.org/10.3389/fmed.2020.602894 https://www.frontiersin.org/articles/10.3389/fmed.2020.602894/full  (Full text)

Paradigm shift to disequilibrium in the genesis of orthostatic intolerance in patients with myalgic encephalomyelitis and chronic fatigue syndrome

Abstract:

Background: Orthostatic intolerance (OI) markedly impairs activities of daily living in patients with myalgic encephalomyelitis (ME) or chronic fatigue syndrome. OI is surmised to be a cardiovascular symptom correlated with cerebral hypo-perfusion and exaggerated sympathetic activation. Postural instability or disequilibrium may be part of the etiology of OI.

Methods: The study comprised 72 patients with ME (18 men, 54 women; mean age, 37 ± 10 years) who underwent neurological examinations and the 10 min standing test. We quantified disequilibrium (instability upon standing with feet together and eyes shut), ability to complete the 10 min standing test, and postural orthostatic tachycardia (POT) during the test.

Results: Disequilibrium was detected in 23/72 (32%) patients and POT in 16 (22%). Nineteen (26%) patients failed to complete the 10 min standing test; disequilibrium was significantly more common in the 19- patient subgroup than in the 53-patient test-completing subgroup (89% vs. 11%, p < 0.01). However, the rate of POT was not different between the groups (21% vs. 23%, p = 1.00). Compared with the 49 (68%) patients without disequilibrium, the 23 (32%) patients with disequilibrium were significantly more likely to have failed to complete the test (74% vs. 4%, p < 0.01). The rate of POT was comparable between the groups (23% vs. 22%, p = 1.00). Among patients with disequilibrium who failed to complete the 10 min standing test and had a previous record, 6/8 had completed the test 6-24 months earlier when all six had reported no disequilibrium.

Conclusion: Disequilibrium should be recognized as an important cause of OI in patients with ME.

Source: Miwa K, Inoue Y. Paradigm shift to disequilibrium in the genesis of orthostatic intolerance in patients with myalgic encephalomyelitis and chronic fatigue syndrome. Int J Cardiol Hypertens. 2020 May 20;5:100032. doi: 10.1016/j.ijchy.2020.100032. PMID: 33447761; PMCID: PMC7803012. https://pubmed.ncbi.nlm.nih.gov/33447761/

The Prospects of the Two-Day Cardiopulmonary Exercise Test (CPET) in ME/CFS Patients: A Meta-Analysis

Abstract:

Background: The diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is problematic due to the lack of established objective measurements. Postexertional malaise (PEM) is a hallmark of ME/CFS, and the two-day cardiopulmonary exercise test (CPET) has been tested as a tool to assess functional impairment in ME/CFS patients. This study aimed to estimate the potential of the CPET.

Methods: We reviewed studies of the two-day CPET and meta-analyzed the differences between ME/CFS patients and controls regarding four parameters: volume of oxygen consumption and level of workload at peak (VO2peak, Workloadpeak) and at ventilatory threshold (VO2@VT, Workload@VT).

Results: The overall mean values of all parameters were lower on the 2nd day of the CPET than the 1st in ME/CFS patients, while it increased in the controls. From the meta-analysis, the difference between patients and controls was highly significant at Workload@VT (overall mean: -10.8 at Test 1 vs. -33.0 at Test 2, p < 0.05), which may reflect present the functional impairment associated with PEM.

Conclusions: Our results show the potential of the two-day CPET to serve as an objective assessment of PEM in ME/CFS patients. Further clinical trials are required to validate this tool compared to other fatigue-inducing disorders, including depression, using well-designed large-scale studies.

Source: Lim EJ, Kang EB, Jang ES, Son CG. The Prospects of the Two-Day Cardiopulmonary Exercise Test (CPET) in ME/CFS Patients: A Meta-Analysis. J Clin Med. 2020 Dec 14;9(12):E4040. doi: 10.3390/jcm9124040. PMID: 33327624. https://pubmed.ncbi.nlm.nih.gov/33327624/

Profile of circulating microRNAs in myalgic encephalomyelitis and their relation to symptom severity, and disease pathophysiology

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic disease, rooted in multi-system dysfunctions characterized by unexplained debilitating fatigue. Post-exertional malaise (PEM), defined as the exacerbation of the patient’s symptoms following minimal physical or mental stress, is a hallmark of ME/CFS. While multiple case definitions exist, there is currently no well-established biomarkers or laboratory tests to diagnose ME/CFS. Our study aimed to investigate circulating microRNA expression in severely ill ME/CFS patients before and after an innovative stress challenge that stimulates PEM. Our findings highlight the differential expression of eleven microRNAs associated with a physiological response to PEM. The present study uncovers specific microRNA expression signatures associated with ME/CFS in response to PEM induction and reports microRNA expression patterns associated to specific symptom severities. The identification of distinctive microRNA expression signatures for ME/CFS through a provocation challenge is essential for the elucidation of the ME/CFS pathophysiology, and lead to accurate diagnoses, prevention measures, and effective treatment options.

Source: Nepotchatykh, E., Elremaly, W., Caraus, I. et al. Profile of circulating microRNAs in myalgic encephalomyelitis and their relation to symptom severity, and disease pathophysiology. Sci Rep 10, 19620 (2020). https://doi.org/10.1038/s41598-020-76438-y  https://www.nature.com/articles/s41598-020-76438-y (Full text)

Characterization of Post-exertional Malaise in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome is characterized by persistent and disabling fatigue, exercise intolerance, cognitive difficulty, and musculoskeletal/joint pain. Post-exertional malaise is a worsening of these symptoms after a physical or mental exertion and is considered a central feature of the illness. Scant observations in the available literature provide qualitative assessments of post-exertional malaise in patients with myalgic encephalomyelitis/chronic fatigue syndrome. To enhance our understanding, a series of outpatient focus groups were convened.

Methods: Nine focus groups totaling 43 patients who reported being diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome were held between November 2016 and August 2019. Focus groups queried post-exertional malaise in daily life and participants’ retrospective memory of post-exertional malaise that followed an exercise provocation with a cardiopulmonary exercise test. Data analysis followed the grounded theory method to systematically code and categorize the data to find meaningful patterns. A qualitative software package was used to move text into categories during data coding.

Results: A wide range of symptoms were attributed to exertion both in daily lives and following cardiopulmonary exercise testing. While three core symptoms emerged (exhaustion, cognitive difficulties, and neuromuscular complaints), participants’ descriptions were notable for their unique individual variations. Of 18 participants who responded to questions centered around symptoms following a cardiopulmonary exercise test, 17 reported that symptoms started within 24 h and peaked in severity within 72 h following the cardiopulmonary exercise test. Patients described post-exertional malaise as interfering with their ability to lead a “normal” life.

Conclusion: The experience of post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome varies greatly between individuals and leads to a diminished quality of life. myalgic encephalomyelitis/chronic fatigue syndrome patients describe post-exertional malaise as all-encompassing with symptoms affecting every part of the body, difficult to predict or manage, and requiring complete bedrest to fully or partially recover. Given the extensive variability in patients, further research identifying subtypes of post-exertional malaise could lead to better targeted therapeutic options.

Source: Stussman B, Williams A, Snow J, Gavin A, Scott R, Nath A, Walitt B. Characterization of Post-exertional Malaise in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Neurol. 2020 Sep 18;11:1025. doi: 10.3389/fneur.2020.01025. PMID: 33071931; PMCID: PMC7530890. https://www.frontiersin.org/articles/10.3389/fneur.2020.01025/full  (Full text)

Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Abstract:

Introduction: In a large study with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients, we showed that 86% had symptoms of orthostatic intolerance in daily life and that 90% had an abnormal reduction in cerebral blood flow (CBF) during a standard tilt test. A standard head-up tilt test might not be tolerated by the most severely affected bed-ridden ME/CFS patients. Sitting upright is a milder orthostatic stress. The present study examined whether a sitting test, measuring cerebral blood flow by extracranial Doppler, would be sufficient to provoke abnormal reductions in cerebral blood flow in severe ME/CFS patients.

Methods and results: 100 severe ME/CFS patients were studied, (88 females) and were compared with 15 healthy controls (HC) (13 females). CBF was measured first while seated for at least one hour, followed by a CBF measurement in the supine position. Fibromyalgia was present in 37 patients. Demographic data as well as supine heart rate and blood pressures were not different between ME/CFS patients and HC. Heart rate and blood pressure did not change significantly between supine and sitting both in patients and HC. Supine CBF was not different between patients and HC. In contrast, absolute CBF during sitting was lower in patients compared to HC: 474 (96) mL/min in patients and 627 (89) mL/min in HC; p < 0.0001. As a result, percent CBF reduction while seated was −24.5 (9.4)% in severe ME/CFS patients and −0.4 (1.2)% in HC (p < 0.0001). In the ten patients who had no orthostatic intolerance complaints in daily life, the CBF reduction was −2.7 (2.1)%, which was not significantly different from HC (p = 0.58). The remaining 90 patients with orthostatic intolerance complaints had a −26.9 (6.2)% CBF reduction. No difference in CBF parameters was found in patients with and without fibromyalgia. Patients with a previous diagnosis of postural orthostatic tachycardia syndrome (POTS) had a significantly larger CBF reduction compared with those without POTS: 28.8 (7.2)% vs. 22.3 (9.7)% (p = 0.0008).

Conclusions: A sitting test in severe ME/CFS patients was sufficient to provoke a clinically and statistically significant mean CBF decline of 24.5%. Patients with a previous diagnosis of POTS had a larger CBF reduction while seated, compared to patients without POTS. The magnitude of these CBF reductions is similar to the results in less severely affected ME/CFS patients during head-up tilt, suggesting that a sitting test is adequate for the diagnosis of orthostatic intolerance in severely affected patients.

Source: C (Linda) MC van Campen, Peter C. Rowe, and Frans C Visser. Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Healthcare 2020, 8(4), 394; https://doi.org/10.3390/healthcare8040394 https://www.mdpi.com/2227-9032/8/4/394/htm (Full text)

Characterization of Post–exertional Malaise in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome is characterized by persistent and disabling fatigue, exercise intolerance, cognitive difficulty, and musculoskeletal/joint pain. Post–exertional malaise is a worsening of these symptoms after a physical or mental exertion and is considered a central feature of the illness. Scant observations in the available literature provide qualitative assessments of post–exertional malaise in patients with myalgic encephalomyelitis/chronic fatigue syndrome. To enhance our understanding, a series of outpatient focus groups were convened.

Methods: Nine focus groups totaling 43 patients who reported being diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome were held between November 2016 and August 2019. Focus groups queried post–exertional malaise in daily life and participants’ retrospective memory of post–exertional malaise that followed an exercise provocation with a cardiopulmonary exercise test. Data analysis followed the grounded theory method to systematically code and categorize the data to find meaningful patterns. A qualitative software package was used to move text into categories during data coding.

Results: A wide range of symptoms were attributed to exertion both in daily lives and following cardiopulmonary exercise testing. While three core symptoms emerged (exhaustion, cognitive difficulties, and neuromuscular complaints), participants’ descriptions were notable for their unique individual variations. Of 18 participants who responded to questions centered around symptoms following a cardiopulmonary exercise test, 17 reported that symptoms started within 24 h and peaked in severity within 72 h following the cardiopulmonary exercise test. Patients described post–exertional malaise as interfering with their ability to lead a “normal” life.

Conclusion: The experience of post–exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome varies greatly between individuals and leads to a diminished quality of life. myalgic encephalomyelitis/chronic fatigue syndrome patients describe post–exertional malaise as all-encompassing with symptoms affecting every part of the body, difficult to predict or manage, and requiring complete bedrest to fully or partially recover. Given the extensive variability in patients, further research identifying subtypes of post–exertional malaise could lead to better targeted therapeutic options.

Source: Stussman Barbara, Williams Ashley, Snow Joseph, Gavin Angelique, Scott Remle, Nath Avindra, Walitt Brian. Characterization of Post–exertional Malaise in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front. Neurol., 18 September 2020 https://www.frontiersin.org/articles/10.3389/fneur.2020.01025/full | https://doi.org/10.3389/fneur.2020.01025 (Full text)

Pain in adolescent chronic fatigue following Epstein-Barr virus infection

Abstract:

Objectives: Acute Epstein-Barr virus (EBV) infection is a trigger of Chronic Fatigue (CF) and Chronic Fatigue Syndrome (CFS). The aim of this cross-sectional study was to investigate pain symptoms and pressure pain thresholds in fatigued and non-fatigued adolescents six months after acute EBV-infection, and in healthy controls. This study is part of the CEBA-project (CF following acute EBV infection in adolescents).

Methods: A total of 195 adolescents (12-20 years old) that had undergone an acute EBV infection six months prior to assessment were divided into fatigued (EBV CF+) and non-fatigued (EBV CF-) cases based on questionnaire score. The EBV CF+ cases were further sub-divided according to case definitions of CFS. In addition, a group of seventy healthy controls was included. Symptoms were mapped with questionnaires. Pressure pain thresholds were measured through pressure algometry. One way ANOVA were used for between-group analyses. Linear regression analyses were used to explore associations between Pediatric Quality of Life (dependent variable), pain symptoms and other variables within the EBV (CF+) group.

Results: The EBV CF+ group had significantly higher scores for pain symptoms as compared with the EBV CF- group and healthy controls, but pressure pain threshold did not differ significantly. The number of pain symptoms as well as pain severity were strongly and independently associated with quality of life.

Conclusions: CF and CFS following acute EBV-infection in adolescents is characterized by high pain symptom burden, which in turn is associated with a decline in quality of life. Pain in CF and CFS is of considerable clinical importance, and should be a focal point for further investigation and intervention in these patient groups.

Source: Brodwall EM, Pedersen M, Asprusten TT, Wyller VBB. Pain in adolescent chronic fatigue following Epstein-Barr virus infection [published online ahead of print, 2020 Sep 7]. Scand J Pain. 2020;/j/sjpain.ahead-of-print/sjpain-2020-0031/sjpain-2020-0031.xml. doi:10.1515/sjpain-2020-0031  https://pubmed.ncbi.nlm.nih.gov/32892183/

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/