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)

Long Term Follow up of Young People With Chronic Fatigue Syndrome Attending a Pediatric Outpatient Service

Abstract:

Aim: To determine the reported duration of illness, the functional and educational long-term outcomes, predictive factors for recovery and seek feedback regarding management in pediatric/adolescent myalgic encepahalomyelitis/chronic fatigue syndrome (ME/CFS).

Methods: A cohort observational study of 784 young people, mean age 14.6 (6-18) years, with ME/CFS diagnosed at a specialist pediatric hospital and receiving regular care, was conducted with follow-up for a mean 8 (range 1-21) years after onset. Baseline symptoms, history, depression and anxiety questionnaires were available from 418. The remaining 366, did not have similar standardized baseline information. Questionnaires requested functional rating, persistent symptoms, duration of illness if “recovered,” social engagement and school/work attendance. Feedback was sought regarding management, support services, useful information, helpful interventions or personnel and use of alternative therapies. Reported recovery and function were compared with baseline information and between the two groups.

Results: Follow-up data were returned from 81.8%. There was no significant difference in functional score (if reported recovery) or illness duration related to provision of baseline data. The mean duration of illness was 5 (range 1-15) years in the 50% who reported recovery. By 5 years 38% and by 10 years 68% reported recovery. At 10 years the mean functional score was 8/10 (range 2-10) with 5% scoring <6. Depression, anxiety or severity of illness at diagnosis was not predictive of non-recovery. Designing and monitoring their own management plan that included educational, social, physical and enjoyable activities, as well as having symptom management and understanding professionals were highly valued. However, remaining engaged in an education system that flexibly accommodated their illness and aspirations was consistently reported as crucial for long term functioning.

Conclusions: ME/CFS in young people has a mean duration of 5 years (1-15) with 68% reporting recovery by 10 years. All improved functionally with 5% remaining very unwell and a further 20% significantly unwell. There were no obvious baseline predictors for recovery. However, depression, anxiety, orthostatic intolerance and to a lesser extent pain at follow up were identified as hampering recovery or function. Supportive professionals, remaining engaged in education and management strategies were identified as helpful.

Source: Rowe KS. Long Term Follow up of Young People With Chronic Fatigue Syndrome Attending a Pediatric Outpatient Service. Front Pediatr. 2019 Feb 21;7:21. doi: 10.3389/fped.2019.00021. eCollection 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393360/ (Full article)

Impaired Health-Related Quality of Life in Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Impact of Core Symptoms

Abstract:

Objective: The objectives of this study were to compare the health-related quality of life (HRQOL) of a North American population of adolescents and young adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to (1) healthy controls (HC), (2) adolescents with ME/CFS in other countries, and (3) other forms of pediatric chronic illness, and (4) to examine the influence of the core illness symptoms in the Institute of Medicine (IOM) case definition on impaired HRQOL.

Study design: Cross-sectional study comparing individuals with ME/CFS referred to a tertiary care Chronic Fatigue clinic and HC. Eligible participants were age 10-30 years and met the Fukuda criteria for CFS. HC were eligible if they were age 10-30 years, with self-reported good, very good, or excellent general health. Pediatric HRQOL was measured using the PedsQL (Pediatric Quality of Life Inventory) and other validated instruments.

Results: We enrolled 55 consecutive ME/CFS patients (46 F) aged 10-23 years. From a pool of 69 potential HC we selected 55 with similar age and gender distribution for comparison. The total and subscale scores on the PedsQL and on all other measures of HRQOL indicated significantly worse function among those with ME/CFS (all P < 0.001). The self-reported frequency of post-exertional malaise (PEM) was significantly associated with the severity of impaired HRQOL (P < 0.001). Cognitive impairment had a weaker association with the PedsQL score (P = 0.02). Orthostatic intolerance was present in 96% of the ME/CFS population. Of the 55 who satisfied the Fukuda criteria, 47 (85%) also satisfied the IOM criteria for the diagnosis. Those meeting the IOM criteria had worse PedsQL total scores than those meeting just the Fukuda criteria (P < 0.001).

Conclusions: HRQOL was substantially lower in an ambulatory population of adolescents and young adults with ME/CFS than for healthy controls in North America, consistent with reports from other continents. HRQOL was also lower in ME/CFS than has been described in children with asthma, diabetes mellitus, epilepsy, eosinophilic gastroenteritis, and cystic fibrosis. The findings of this study lend further support to the inclusion of PEM, cognitive impairment, and orthostatic intolerance as core symptoms of pediatric ME/CFS.

Source: Roma M, Marden CL, Flaherty MAK, Jasion SE, Cranston EM, Rowe PC. Impaired Health-Related Quality of Life in Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Impact of Core Symptoms. Front Pediatr. 2019 Feb 15;7:26. doi: 10.3389/fped.2019.00026. eCollection 2019. https://www.ncbi.nlm.nih.gov/pubmed/30828572

Blood Volume Status in ME/CFS Correlates With the Presence or Absence of Orthostatic Symptoms: Preliminary Results

Abstract:

Introduction: Conflicting data have been published on the reduction of circulating blood volume in adults with Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The aim of the present study was to compare blood volumes based on the presence or absence of orthostatic symptoms.

Methods and results: Twenty consecutive adults with ME/CFS participated in the study. All underwent dual isotope blood volume measurement and were evaluated for a clinical suspicion of orthostatic intolerance (OI). The mean age was 34 (10) years, and median duration of disease was 7.5 (6-10) years. The mean (SD) absolute blood volume was 59 (8) ml/kg, a value -11 (7) ml/kg below the reference blood volume. Of the 12 patients, 4 had no OI and 8 had a clinical suspicion of OI. In 8 patients with OI, absolute blood volumes were significantly lower than for the 4 without OI (56 [2] vs. 66 [5]; p < 0.05) as were the differences between the measured and the reference blood volume (-14 [2]; vs. -4 [3]; p < 0.02).

Conclusions: Adults with ME/CFS had a significantly lower blood volume if they had a clinical suspicion of OI compared to those without a clinical suspicion of OI, as well as a significantly lower blood volume compared to the expected value. The data suggest that accounting for symptoms of OI could enhance the detection of the subset with reduced blood volume.

Source: van Campen CLMC1, Rowe PC2, Visser FC1. Blood Volume Status in ME/CFS Correlates With the Presence or Absence of Orthostatic Symptoms: Preliminary Results. Front Pediatr. 2018 Nov 15;6:352. doi: 10.3389/fped.2018.00352. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262290/ (Full article)

Low Sensitivity of Abbreviated Tilt Table Testing for Diagnosing Postural Tachycardia Syndrome in Adults With ME/CFS

Abstract:

Introduction: Orthostatic intolerance is common among individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In some ME/CFS case definitions, orthostatic intolerance is considered a core feature of the disorder. Some studies have employed tilt table tests lasting 2-5 min to diagnose one common form of orthostatic intolerance, postural tachycardia syndrome (POTS). We examined the diagnostic yield of abbreviated durations of tilt testing in adults meeting criteria for ME/CFS, and identified the proportion with POTS misdiagnosed using testing of <10 min.

Methods: Eligible participants were consecutive individuals satisfying study criteria for ME/CFS and POTS evaluated at the Stichting CardioZorg (SCZ, Hoofddorp, NL) between November 2012 and August 2018. Individuals being treated with medications commonly used to manage orthostatic intolerance were excluded. Head-up tilt table testing involved 15 min of supine posture then 20 min at 70 degrees upright. Only the data from the first 10-min upright were used. POTS was defined as an increase in HR during a maximum of 10 min of upright tilt of at least 30 beats per minute (bpm), in the absence of either classical or delayed orthostatic hypotension. We measured the time until HR criteria for POTS were reached using survival curves, and compared survival curves between subgroups divided by age, sex, disease duration, and degree of hypocapnia during the test.

Results: Of 627 individuals with ME/CFS evaluated during the study period, 155 met criteria for POTS. The median time to reaching HR criteria for POTS was 3 min. A two-minute tilt table test would miss 55% (95% CI, 48-63%) of those meeting POTS criteria over the course of 10 min upright. The median time to reaching HR criteria for POTS did not differ by sex, age, duration of ME/CFS, or hypocapnia during tilt.

Conclusions: Abbreviated tilt table testing misses a substantial proportion of those ultimately diagnosed with POTS during a 10-min tilt table test, and should be abandoned for the clinical diagnosis and in epidemiologic studies designed to estimate the prevalence of POTS among those with ME/CFS.

Source: van Campen CLMC, Rowe PC, Visser FC. Low Sensitivity of Abbreviated Tilt Table Testing for Diagnosing Postural Tachycardia Syndrome in Adults With ME/CFS. Front Pediatr. 2018 Nov 16;6:349. doi: 10.3389/fped.2018.00349. eCollection 2018. https://www.ncbi.nlm.nih.gov/pubmed/30505831

Two-Year Follow-Up of Impaired Range of Motion in Chronic Fatigue Syndrome

Abstract:

OBJECTIVE: To measure changes in range of motion (ROM) over time in a cohort of 55 adolescents and young adults with chronic fatigue syndrome and to determine whether changes in ROM correlated with changes in health-related quality of life.

STUDY DESIGN: Participants underwent a standardized examination of 11 areas of limb and spine ROM at baseline and at 3- to 6-month intervals for 2 years, resulting in a ROM score that ranged from 0 (normal throughout) to 11 (abnormal ROM in all areas tested). We measured the time until the ROM score was ≤2 (the score in healthy age-matched controls). Change in ROM was measured by subtracting the 24-month from the baseline ROM score and by summing the degrees of change in the 10 tests with continuous outcomes. Health-related quality of life was measured using the Pediatric Quality of Life Inventory 4.0 (PedsQL).

RESULTS: The mean age at enrollment was 16.5 years (range 10-23). Two-year follow-up was available for 53 (96%). The proportion with a ROM score of >2 fell gradually over 2 years, from 78% at entry to 20% at 24 months (P < .001). ROM scores improved from a median of 5 at entry to 2 at 24 months (P < .001). The change in the summed degrees of improvement in ROM correlated positively with improvement in the PedsQL physical function subscale (r = 0.30; P < .03).

CONCLUSIONS: In association with multimodal therapy, young people with chronic fatigue syndrome experienced progressively less impairment in ROM over 2 years, correlating with improvements in the physical function subscale of the PedsQL.

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Source: Rowe PC, Marden CL, Flaherty MAK, Jasion SE, Cranston EM, Fontaine KR, Violand RL. Two-Year Follow-Up of Impaired Range of Motion in Chronic Fatigue Syndrome. J Pediatr. 2018 Jun 1. pii: S0022-3476(18)30659-0. doi: 10.1016/j.jpeds.2018.05.012. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29866593

Improvement of severe myalgic encephalomyelitis/chronic fatigue syndrome symptoms following surgical treatment of cervical spinal stenosis

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a potentially disabling disorder. Little is known about the contributors to severe forms of the illness. We describe three consecutive patients with severe ME/CFS whose symptoms improved after recognition and surgical management of their cervical spinal stenosis.

Methods: All patients satisfied clinical criteria for ME/CFS and orthostatic intolerance, and were later found to have cervical spinal stenosis. Overall function was assessed before and after surgery using the Karnofsky score and the SF-36 physical function subscale score.

Results: Neurological findings included > 3+ deep tendon reflexes in 2 of 3, a positive Hoffman sign in 2 of 3, tremor in 2 of 3, and absent gag reflex in 1 of 3. The cervical spine canal diameter in the three patients ranged from 6 to 8.5 mm. One had congenital cervical stenosis with superimposed spondylosis, and two had single- or two-level spondylosis. Anterior cervical disc replacement surgery in two patients and a hybrid anterior cervical disc fusion and disc replacement in the third was associated with a marked improvement in myelopathic symptoms, resolution of lightheadedness and hemodynamic dysfunction, improvement in activity levels, and improvement in global ME/CFS symptoms.

Conclusions: The prompt post-surgical restoration of more normal function suggests that cervical spine stenosis contributed to the pathogenesis of refractory ME/CFS and orthostatic symptoms. The improvements following surgery emphasize the importance of a careful search for myelopathic examination findings in those with ME/CFS, especially when individuals with severe impairment are not responding to treatment.

Source: Rowe, P.C., Marden, C.L., Heinlein, S. et al. J Transl Med (2018) 16: 21. https://doi.org/10.1186/s12967-018-1397-7

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease that affects children and adolescents as well as adults. The etiology has not been established. While many pediatricians and other health-care providers are aware of ME/CFS, they often lack essential knowledge that is necessary for diagnosis and treatment. Many young patients experience symptoms for years before receiving a diagnosis.

This primer, written by the International Writing Group for Pediatric ME/CFS, provides information necessary to understand, diagnose, and manage the symptoms of ME/CFS in children and adolescents. ME/CFS is characterized by overwhelming fatigue with a substantial loss of physical and mental stamina. Cardinal features are malaise and a worsening of symptoms following minimal physical or mental exertion. These post-exertional symptoms can persist for hours, days, or weeks and are not relieved by rest or sleep.

Other symptoms include cognitive problems, unrefreshing or disturbed sleep, generalized or localized pain, lightheadedness, and additional symptoms in multiple organ systems. While some young patients can attend school, on a full or part-time basis, many others are wheelchair dependent, housebound, or bedbound.

Prevalence estimates for pediatric ME/CFS vary from 0.1 to 0.5%. Because there is no diagnostic test for ME/CFS, diagnosis is purely clinical, based on the history and the exclusion of other fatiguing illnesses by physical examination and medical testing. Co-existing medical conditions including orthostatic intolerance (OI) are common.

Successful management is based on determining the optimum balance of rest and activity to help prevent post-exertional symptom worsening. Medications are helpful to treat pain, insomnia, OI and other symptoms. The published literature on ME/CFS and specifically that describing the diagnosis and management of pediatric ME/CFS is very limited. Where published studies are lacking, recommendations are based on the clinical observations and practices of the authors.

Source: Rowe PC, Underhill RA, Friedman KJ, Gurwitt A, Medow MS, Schwartz MS, Speight N, Stewart JM, Vallings R, Rowe KS. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer. Front Pediatr. 2017 Jun 19;5:121. doi: 10.3389/fped.2017.00121. eCollection 2017. http://journal.frontiersin.org/article/10.3389/fped.2017.00121/full

Chronic fatigue syndrome flare-ups caused by straining muscles and nerves

A recent study conducted by researchers at the University of Alabama at Birmingham and Johns Hopkins University School of Medicine published in PLOS ONE shows that symptoms of chronic fatigue syndrome, a complex and disabling multisystem disorder, can be provoked by imposing a mild to moderate strain to the muscles and nerves.

Eighty individuals, 60 with CFS and 20 without CFS, reported their levels of fatigue, body pain, lightheadedness, concentration difficulties and headache every five minutes while undergoing 15 minutes of either a passive supine straight leg raise — the raising and holding up of one of an individual’s legs while they lie on their back on an exam table — or a sham leg raise that did not cause strain.

Participants were contacted 24 hours later and again reported their symptoms. Compared to those with CFS who underwent the sham leg raise, individuals with CFS who underwent the passive leg raise that actually strained their muscles and nerves reported significantly increased body pain and concentration difficulties during the procedure. After 24 hours, these same individuals who underwent the true strain also reported greater symptom intensity for lightheadedness and the overall combined score for symptoms. The individuals with CFS who underwent the true strain also reported more symptoms during, and 24 hours after, the true strain compared to individuals without CFS.

“These findings have practical implications for understanding why exercise and the activities of daily living might be capable of provoking CFS symptoms,” said Kevin Fontaine, Ph.D., professor and chair of the UAB School of Public Health Department of Health Behavior and a co-author of the paper. “If simply holding up the leg of someone with CFS to a degree that produces a mild to moderate strain is capable of provoking their symptoms, prolonged or excessive muscle strain beyond the usual range of motion that occurs during daily activities might also produce symptom flares.”

As Peter Rowe, M.D., lead author and director of Johns Hopkins Children’s Center Chronic Fatigue Clinic, noted in the article, “The lengthwise strain applied to the nerves and muscles of the lower limb is capable of increasing symptom intensity in individuals with CFS for up to 24 hours, indicating that increased mechanical sensitivity may be a contributor to the provocation of symptoms in this disorder.”

Rowe and Fontaine, and their physical therapist collaborator Rick Violand, intend to extend this work to further understand the effects that strains to the muscles and nerves have on CFS, as well as whether specific physical therapy methods could be used to improve neuromuscular function to reduce symptoms.

Journal Reference: Peter C. Rowe, Kevin R. Fontaine, Megan Lauver, Samantha E. Jasion, Colleen L. Marden, Malini Moni, Carol B. Thompson, Richard L. Violand. Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome. PLOS ONE, 2016; 11 (7): e0159386 DOI: 10.1371/journal.pone.0159386

 

Source: University of Alabama at Birmingham. “Chronic fatigue syndrome flare-ups caused by straining muscles and nerves.” ScienceDaily. ScienceDaily, 18 July 2016. https://www.sciencedaily.com/releases/2016/07/160718194125.htm