Tag: symptoms

Assessment of symptoms in myalgic encephalomyelitis/chronic fatigue syndrome: a comparative study of existing scales

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifaceted disorder characterized by persistent fatigue, post-exertional malaise (PEM), cognitive dysfunction, sleep disturbance, pain, psychological distress, orthostatic intolerance, and impaired multidimensional health status and functioning. In the absence of reliable biomarkers, standardized symptom assessment is essential for accurate diagnosis and comparability across studies.

This narrative literature review synthesized studies identified through PubMed and Web of Science up to June 2024, covering assessment instruments across major ME/CFS symptom domains. Tools were evaluated for their psychometric validity, clinical applicability, and key limitations.

Overall, existing scales demonstrate acceptable reliability but vary in sensitivity and disease specificity. Harmonized, multidimensional, and digitally or objectively validated measures are needed to improve diagnostic precision, longitudinal monitoring, and clinical translation in ME/CFS.

Source: Lu J, Sun W, Li S, Qu Y, Liu T, Guo S, Feng C, Yang T. Assessment of symptoms in myalgic encephalomyelitis/chronic fatigue syndrome: a comparative study of existing scales. Front Neurol. 2025 Nov 18;16:1618272. doi: 10.3389/fneur.2025.1618272. PMID: 41341517; PMCID: PMC12668935. https://pmc.ncbi.nlm.nih.gov/articles/PMC12668935/ (Full text)

Systematic literature review: treatment of postural orthostatic tachycardia syndrome (POTS)

Abstract:

Postural orthostatic tachycardia syndrome (POTS) is a condition defined by symptoms of orthostatic intolerance and a sustained heart rate (HR) increment of ≥ 30 beats per minute (bpm) upon postural change to the upright position in the absence of orthostatic hypotension, defined as a sustained decrease in systolic blood pressure (SBP) of ≥ 20 mmHg or a decrease in diastolic blood pressure (DBP) of ≥ 10 mmHg within 3 min of standing. In children, a sustained HR increment of at least 40 bpm is required for diagnosis of POTS. POTS is a common condition in adults and children suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In daily clinical practice, therapeutic recommendations are rare and evidence is missing.

The objective of this review is to present the current knowledge on non-pharmacological and pharmacological approaches in POTS with a special focus on POTS therapy in children and people with ME/CFS. Of 3853 studies, 45 studies were included in the systematic review.

on therapy in POTS is rare and large randomized controlled trials (RCT) on single interventions are needed. Non-pharmacological approaches such as the use of compression garments, physical training, salt supplementation and transdermal vagal nerve stimulation could be possible treatment options in POTS because they are easy to implement as first-line therapeutic measures in clinical practice. For pharmaceuticals, several studies showed significant effects following therapy with ivabradine and β-adrenergic blocking agents. There are single studies which imply that midodrine (hydrochloride) and pyridostigmine seem to have a beneficial effect on hemodynamics in POTS.

Source: Schiweck N, Langer K, Maier A, Vilser D, Spiegler J. Systematic literature review: treatment of postural orthostatic tachycardia syndrome (POTS). Clin Auton Res. 2025 Nov 12. doi: 10.1007/s10286-025-01172-2. Epub ahead of print. PMID: 41225175. https://link.springer.com/article/10.1007/s10286-025-01172-2 (Full text)

The association of fatigue and pain with cognitive test performance in patients with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Objectives: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) typically perform worse on cognitive tasks compared to controls. The present study explored the independent associations of fatigue and pain symptoms with cognitive performance in a large sample of patients who met CDC criteria of CFS (n = 1375), of whom most also met NICE/ IOM criteria (n = 1072). Moreover, we tested the hypothesis that these associations become stronger with older age and longer symptom duration.

Methods: Questionnaires and diaries were employed assessing fatigue and pain severity, together with the impact of health problems on daily life (using the SF-36 ‘Physical Functioning’ and ‘Bodily Pain’ subscales). Cognitive outcomes consisted of speeded performance measures, namely the Symbol Digit Test, motor speed, simple and choice reaction time (RT), and response inhibition. Categorical regression with lasso penalization was employed to identify relevant correlates of cognitive performance.

Results: Fatigue severity remained as only correlate of response inhibition. For the other cognitive outcomes, fatigue severity consistently emerged together with contributions of pain severity, bodily pain and/or physical functioning. Restricting these analyses to those patients meeting NICE/IOM criteria revealed overall similar results. Age, not symptom duration, moderated several relationships, showing more pronounced associations between cognitive performance and pain severity, physical functioning, and bodily pain with older age.

Conclusions: This study highlights that a multidimensional nature of symptoms, including fatigue and pain severity, and the impact on daily-life functioning, relate to lower cognitive performance in patients with ME/CFS. Studies are needed to identify the direction and potential causality of these associations.

Source: Oosterman JM, van der Schaaf M, de Kleijn WPE, Kuut TA, Brazil IA, Knoop H. The association of fatigue and pain with cognitive test performance in patients with myalgic encephalomyelitis/chronic fatigue syndrome. J Psychosom Res. 2025 Oct 3;199:112401. doi: 10.1016/j.jpsychores.2025.112401. Epub ahead of print. PMID: 41101039. https://www.sciencedirect.com/science/article/pii/S0022399925003654 (Full text)

Improvement in Upper Limb and Systemic Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Symptoms After Surgical Treatment of Neurogenic Thoracic Outlet Syndrome

Abstract:

Thoracic outlet syndrome (TOS) is characterized by compression of nerves or blood vessels as they pass through the scalene triangle and the costoclavicular space, and under the pectoralis minor. Common symptoms include arm fatigue and heaviness, paresthesias, and neck and upper back pain, provoked by arm extension or elevation.

We have recently reported that some myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients report symptoms suggestive of TOS, specifically with respect to overhead activity, but there is uncertainty whether this overlap in symptoms is more related to ME/CFS itself or a direct contribution by TOS. This case report describes an ME/CFS patient diagnosed with TOS, who experienced major decreases in many expected and unexpected symptoms after bilateral TOS surgery.

A 19-year-old female patient with ME/CFS and the hypermobile Ehlers-Danlos syndrome (hEDS) developed progressive symptoms of numbness and tingling in the upper limbs, which did not improve after two months of physical therapy. The patient elected to undergo the rib resection with neurolysis and scalenectomy surgery on her left side. Due to the success in the reduction of symptoms, she elected to undergo the same procedure on the right side three months later.

By eight weeks after the second surgery, the patient had experienced an expected complete resolution of upper limb numbness and tingling. She also reported a complete resolution of migraines, occipital neuralgia, vertigo, and visual disturbances, along with a marked improvement in cognitive fogginess and lightheadedness.

This case report highlights the potential for marked improvements in clinical function after recognition and surgical treatment of TOS in a patient with comorbid hEDS and ME/CFS. In addition to expected improvement in upper limb symptoms and the resolution of occipital headaches, our patient noted improvement in systemic symptoms of lightheadedness, cognitive dysfunction, and visual disturbances.

This experience suggests that those with hEDS and ME/CFS should be more carefully screened for brachial plexus dysfunction. Conversely, ascertainment of systemic symptoms may enhance the diagnosis of TOS and the items assessed in surgical treatment outcome studies.

Source: Christoforou ME, Lum YW, Sroge SC, Azola AM, Rowe PC. Improvement in Upper Limb and Systemic Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Symptoms After Surgical Treatment of Neurogenic Thoracic Outlet Syndrome. Cureus. 2025 Aug 19;17(8):e90494. doi: 10.7759/cureus.90494. PMID: 40978926; PMCID: PMC12445393. https://pmc.ncbi.nlm.nih.gov/articles/PMC12445393/ (Full text)

Hormonal Fluctuations and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Women: The Role of Menstrual Cycle and Menopause

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling multisystem disease, predominantly affecting women as compared to men and showing extreme symptom variability across reproductive life stages. The aim of this research was to determine the effects of hormonal changes, menopause status, and symptom severity in individuals with ME/CFS.

This was a prospective observational cohort study conducted at JPMC, Karachi from January 2024 to June 2025. Final recruitment was of 150 women with ME/CFS (90 were in the premenopausal, 30 in the perimenopausal and 30 in the postmenopausal strata). Baseline demographic and clinical profiling, laboratory hormonal assays (estradiol, progesterone, LH, FSH), symptom daily profiles and monthly activity data, and objective autonomic probe reflex testing (tilt-table studies) were obtained.

The findings revealed a clear hormonal gradient across the groups (ANOVA p < 0.001), with estradiol and progesterone levels becoming lower and gonadotropins higher with older reproductive age.

Symptom trajectories varied according to for premenopausal women: fatigue and pain peaked pre menstrually (CFQ p = 0.01, VAS p = 0.02) and cognitive impairment was lowest at ovulation (p = 0.04).

When comparing across menopause groups, symptom burden was greater in the perimenopausal and postmenopausal participants and the perimenopausal and postmenopausal participants had lower SF-36 quality-of-life component scores (physical functioning 0.01, mental health 0.04).

Tilt-table findings from the cohort suggest age-related differences in autonomic dysfunction with postmenopausal women more likely to exhibit orthostatic hypotension (36.7%) and premenopausal women more likely to express POTS (38.9%).

The correlation analysis revealed that low levels of estradiol and progesterone were significantly correlated with higher levels of fatigue and pain, whereas the opposite association was found for LH and FSH, the latter two being positively correlated with fatigue and orthostatic symptoms.

These findings provide the first quantifiable evidence for reproductive hormonal dynamics substantially modulating the clinical expression of ME/CFS in women and the need for hormone-sensitive management approaches.

Source: Mehak Khan, Sidra Anees, Muhammad Muthar Anees, Komal Khalid Chaudhry, Syeda Marium Rashid Zaidi, Vishan Das, Rimal Rashid. Hormonal Fluctuations and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Women: The Role of Menstrual Cycle and Menopause. The Research of Medical Science Review; Volume 3, Issue 8, 2025. ISSN: 3007-1208 & 3007-1216. https://medscireview.net/index.php/Journal/article/view/2032 (Full text available as PDF file)

Autonomic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Findings from the Multi-Site Clinical Assessment of ME/CFS (MCAM) Study in the USA

Abstract:

Background/Objectives: Symptoms of autonomic dysfunction are common in infection-associated chronic conditions and illnesses (IACCIs), including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This study aimed to evaluate autonomic symptoms and their impact on ME/CFS illness severity.
Methods: Data came from a multi-site study conducted in seven ME/CFS specialty clinics during 2012–2020. Autonomic dysfunction was assessed using the Composite Autonomic Symptom Scale 31 (COMPASS-31), medical history, and a lean test originally described by the National Aeronautics and Space Administration (NASA). Illness severity was assessed using Patient-Reported Outcomes Measurement Information System measures, the 36-item short-form, as well as the CDC Symptom Inventory. This analysis included 442 participants who completed the baseline COMPASS-31 assessment, comprising 301 individuals with ME/CFS and 141 healthy controls (HC).
Results: ME/CFS participants reported higher autonomic symptom burden than HC across three assessment tools (all p < 0.0001), including the COMPASS-31 total score (34.1 vs. 6.8) and medical history indicators [dizziness or vertigo (42.6% vs. 2.8%), cold extremities (38.6% vs. 5.7%), and orthostatic intolerance (OI, 33.9% vs. 0.7%)]. Among ME/CFS participants, 97% had at least one autonomic symptom. Those with symptoms in the OI, gastrointestinal, and pupillomotor domains had significantly higher illness severity than those without these symptoms.
Conclusions: ME/CFS patients exhibit a substantial autonomic symptom burden that correlates with greater illness severity. Individualized care strategies targeting dysautonomia assessment and intervention may offer meaningful improvements in symptom management and quality of life for those with ME/CFS and similar chronic conditions.
Source: Issa A, Lin J-MS, Chen Y, Attell J, Brimmer D, Bertolli J, Natelson BH, Lapp CW, Podell RN, Kogelnik AM, et al. Autonomic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Findings from the Multi-Site Clinical Assessment of ME/CFS (MCAM) Study in the USA. Journal of Clinical Medicine. 2025; 14(17):6269. https://doi.org/10.3390/jcm14176269  https://www.mdpi.com/2077-0383/14/17/6269 (Full text)

Causes of symptoms and symptom persistence in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Debilitating symptoms for many years can follow acute COVID-19 (“long COVID”), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and various post-acute infection syndromes (PAISs). Together, long COVID and ME/CFS affect 60-400 million individuals, globally. Many similar underlying biological abnormalities have been identified in both conditions including autoantibodies against neural targets, endothelial dysfunction, acquired mitochondrial dysfunction, and a pro-inflammatory gut microbiome. Each of these abnormalities may directly cause some of the symptoms.

In addition, the symptoms also may be caused by ancient, evolutionarily conserved symptomatic and metabolic responses to vital threats-sickness behavior and torpor-responses mediated by specific, recently discovered neural circuits. These neural circuits constitute a symptom-generating pathway, activated by neuroinflammation, which may be targeted by therapeutics to quell neuroinflammation.

Many factors cause the symptoms to become chronic, including persistent infectious agents (and/or their nucleic acids and antigens) and the fact that many of the underlying biological abnormalities reinforce each other, creating ongoing physiological vicious cycles.

Source:Komaroff AL, Dantzer R. Causes of symptoms and symptom persistence in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome. Cell Rep Med. 2025 Jul 25:102259. doi: 10.1016/j.xcrm.2025.102259. Epub ahead of print. PMID: 40744021. https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00332-5 (Full text)

Growing recognition of post-acute infection syndromes

Commentary:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID affect large numbers of people, and constitute a substantial burden to the U.S. and global economies. The article by Eckey et al., in this issue of PNAS (1), adds to the growing evidence that the two illnesses have much in common. Moreover, the illnesses may represent just two examples of an even larger, recently recognized class of illness: post-acute infection syndromes (PAIS) (2).
ME/CFS
This illness first attracted attention in the 1980s. Typically, people suffering from ME/CFS previously have been healthy, and then develop a flu-like illness. While that illness appears initially not unlike previous transient illnesses, and while the respiratory symptoms and fever usually improve, people are left with a severe, persisting fatigue, cognitive problems, worsened symptoms following physical or mental exertion or upright posture, as well as unrefreshing sleep, an illness that can last for years (3, 4). The symptoms are not relieved by rest, and greatly impair a person’s ability to function at work and at home. Some individuals are homebound, some largely bedbound. People with ME/CFS often say, in so many words, “I am no longer the person I was.”
In the 1980s, some scientists suspected that a novel human pathogen was causing the illness. Such speculation seemed reasonable, since a novel virus recently had been discovered to cause the AIDS. However, no single, novel pathogen has emerged as the cause of ME/CFS.
Moreover, the standard laboratory tests that were performed in the 1980s generally came back “normal,” leading some to believe there were no underlying biological abnormalities to explain the symptoms. However, over the past 40 y, thousands of studies have identified many underlying abnormalities involving the brain, immune system, energy metabolism, redox imbalance, vascular injury, and gut microbiota (4–9). The symptoms of the illness are, indeed, accompanied by objective abnormalities.
Despite the fact that—in the United States, alone—the illness is estimated to affect up to 3.1 million people, and to generate direct and indirect expenses of approximately $36 to 51 billion annually (3, 10), relatively few investigators have sought to study the illness: the initial skepticism about whether the illness had a biological basis may have created a lingering stigma. That skepticism faded, to some degree, following publication in 2015 of a report from the U.S. National Academies of Science, Engineering and Medicine highlighting the importance of the problem (3).
Long COVID
Then, along came the COVID-19 pandemic. It was predicted that the pandemic would greatly increase the number of people with an ME/CFS-like illness (11), and that has proved to be the case. Many who have “recovered” from acute COVID-19, even from mild cases, have developed a persisting illness (called “long COVID”) with symptoms much like ME/CFS. The cumulative global incidence of long COVID may be as high as 400 million individuals (5, 8), and the costs to the U.S. and global economy (not including the direct costs of healthcare) may be several trillion dollars in the next 5 to 10 y (8, 12).
Comparing ME/CFS and Long COVID
The similarity of the symptoms seen in ME/CFS and long COVID is underscored by the report from Eckey et al. (1). The study involved a survey of nearly 4,000 people with these illnesses. Participants recorded the prevalence and severity of a large number of symptoms, comorbid illnesses, and responses to different treatments.
The authors recognize that such a survey has important limitations. The diagnoses of ME/CFS, long COVID, and comorbid illnesses were self-reported, and not determined by protocol-directed objective testing—although such testing often had been performed by their doctors. Likewise, the responses to different treatments were self-reported, not the results of randomized, placebo-controlled trials. Nevertheless, the large number of study subjects, and the consistency of their responses, suggests that their responses are valid.
Symptoms.
As seen in figure 1 of the report by Eckey et al. (1), the frequency of each of the symptoms is very similar in both illnesses. At the same time, there may be subgroups of people with both ME/CFS and long COVID in whom different symptoms are predominant: it is possible that these subgroups have different underlying pathophysiology, responses to treatments, and prognosis.
Underlying Pathophysiology.
Of course, the fact that the symptoms and symptom frequency are similar does not necessarily mean the two illnesses share an underlying pathophysiology. Nevertheless, it appears that they do. A detailed analysis of the underlying biological abnormalities seen in both illnesses reveals a striking similarity (6).
Comorbid Diseases.
The survey conducted by Eckey et al., addressed two other dimensions by which to compare the two illnesses. First, the survey found that people with the two illnesses frequently had the same comorbid conditions, particularly postural orthostatic tachycardia syndrome (POTS), migraine, dysautonomia, anxiety and depression, mast cell activation syndrome (MCAS), Ehlers–Danlos syndrome (EDS)/joint hypermobility, and attention deficit disorder (ADD) (1).

Response to Therapies.

Patients with the two illnesses also responded similarly to specific treatments. Remarkably, even at the level of specific symptoms, responses were similar in people with the two illnesses, and the drugs most effective against particular symptoms would be expected to improve those symptoms, adding credibility to the self-reported improvement (1). Thus, the study is consistent with others in finding similar symptoms in people with the two illnesses and, additionally, finds similar comorbidities and responses to treatment.

PAIS

ME/CFS and long COVID are not the only two illnesses that share very similar symptoms. Over the past century, there have been many reports of an illness with very similar symptoms following multiple different acute bacterial, viral, fungal, and protozoal infections; hence, the proposal to call all of these illnesses PAIS (2). Long COVID surely is a PAIS (since the inciting infectious agent is known), and myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) likely often is (even though the inciting agents often have not been pursued by physicians).

IACIs
PAIS, in turn, are one example of an even larger umbrella category, a group of disorders called IACIs (9, 13). As shown in Fig. 1, we distinguish three categories of IACIs: new organ injury from an infectious agent, such as the development of multiple sclerosis following primary infection with Epstein–Barr virus or duodenal ulcers caused by Helicobacter pylori; accelerated incidence of disease processes that had not yet become apparent before the time of an acute infection (including accelerated atherosclerosis and neurodegeneration post-COVID) (8, 14); and PAIS. Some observers use the term long COVID to include all three categories of illness following acute infection with SARS-CoV-2. We restrict the use of the term long COVID to just the PAIS that can follow SARS-CoV-2 infection.
Read the rest of this article here: https://www.pnas.org/doi/10.1073/pnas.2513877122
Source: A.L. Komaroff, Growing recognition of post-acute infection syndromes, Proc. Natl. Acad. Sci. U.S.A. 122 (29) e2513877122, https://doi.org/10.1073/pnas.2513877122 (2025). https://www.pnas.org/doi/10.1073/pnas.2513877122 (Full text)

A Signal for Voice and Speech Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background/Objectives: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may report abnormalities in voice and speech; however, no formal research has been conducted in this area.
Methods: An online mixed-methods survey was completed by 685 people with ME/CFS. A total of 302 respondents completed the qualitative component (44.09%). Questions assessed disease experience with ME/CFS and post-exertional malaise without prompting on specific symptoms. Within the qualitative results, a search of the terms “speech, voice,” “words,” and “speak” was conducted.
Results: Excluding neurocognitive associations, colloquial phrases, and “speech therapy,” there were 38 mentions of the terms in the context of voice or speech changes across 28 unique qualitative survey responses (9.27%).
Conclusions: A notable portion of respondents reported voice or speech changes when responding to open-ended qualitative questions about their disease experience. More research is needed regarding the implications of voice and speech anomalies in ME/CFS pathology and disease monitoring.
Source: Grach SL, Seltzer J, Orbelo DM. A Signal for Voice and Speech Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Journal of Clinical Medicine. 2025; 14(14):4847. https://doi.org/10.3390/jcm14144847 https://www.mdpi.com/2077-0383/14/14/4847 (Full text)

Two Neurocognitive Domains Identified for Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-Acute Sequelae of COVID-19

Abstract:

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-Acute Sequelae of COVID-19 (PASC) often have neurocognitive complaints that involve memory and concentration problems and difficulties paying attention. Other neurocognitive domains such as hypersensitivity to noise and light have rarely been included as aspects of neurocognitive impairment for these post-viral conditions.

The current study evaluated a more extensive list of neurocognitive items for a group of 2,313 patients with ME/CFS and 299 patients with PASC. Exploratory factor analyses found two factors for each patient group, one involving classic memory and concentration symptoms and the other involving sensory overload phenomena. The findings suggest that researchers might consider expanding the types of self-report neurocognitive symptoms among patients with these post-viral illnesses.

Source: Ariadna E Sandoval, Mingqi Li, Leonard A. Jason. Two Neurocognitive Domains Identified for Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-Acute Sequelae of COVID-19. Front. Neurol., Sec. Cognitive and Behavioral Neurology, Volume 16 – 2025 | doi: 10.3389/fneur.2025.1612548 https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1612548/abstract