Tag: dysautonomia

Understanding concussion in myalgic encephalomyelitis/chronic fatigue syndrome: Findings from the 2023 National Health Interview study

Abstract:

Background: Although myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms (dysautonomia, dizziness, balance impairments) may theoretically contribute to an association with concussion, the nature of this association has not been determined. This study explored the association between ME/CFS and concussion, as well as risk factors for concussion, history of recent falls, and feelings of being dizzy or off balance.

Method: 2023 National Health Interview Survey data were utilized. United States adults (unweighted N = 29,373) responded to items regarding sociodemographic factors, ME/CFS status, and history of concussion, falls, and feeling off balance or dizzy. Logistic regression analyses assessed the association between ME/CFS and concussion, falls, and feeling dizziness or balance problems within the past year, adjusting for sociodemographic factors.

Results: Individuals with ME/CFS had 4.89 times greater odds of reporting concussion in the past year compared to individuals without ME/CFS. Individuals with ME/CFS also had 2.86 times greater odds of having fallen within the past year and 5.88 times greater odds of reporting feeling dizzy or off balance in the past year.

Conclusions: ME/CFS status may be associated with concussion status. Healthcare practitioners should improve concussion screening and referrals for reducing concussion risk among individuals with ME/CFS.

Source: Sirotiak Z, Adamowicz JL, Thomas EBK. Understanding concussion in myalgic encephalomyelitis/chronic fatigue syndrome: Findings from the 2023 National Health Interview study. Brain Inj. 2025 Oct 16:1-8. doi: 10.1080/02699052.2025.2575479. Epub ahead of print. PMID: 41103060. https://pubmed.ncbi.nlm.nih.gov/41103060/

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)

Beneficial effects of intermittent intravenous saline infusion in dysautonomic patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a caseseries

Abstract:

Purpose. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition with no single, uniformly effective pharmacologic therapy. Dysautonomic features like orthostatic intolerance and postural tachycardia syndrome are common features in ME/CFS, severely affecting the patient´s quality-of-life. Intermittent saline infusion may reduce symptoms associated with dysautonomia, but this has not been tested scientifically in patients with ME/CFS.

In this case-series, 22 patients with ME/CFS and signs of dysautonomia and/or hypovolemia were treated every third week over 9 weeks with intravenous saline (9 mg/mL NaCl), using standard aseptic technique. Symptoms were monitored throughout the treatment regime, and a follow-up evaluation was conducted.

Results. At treatment start, patients were predominantly female (95%), at mean age 46 ± 10 years, and with a mean body hydration percentage of 48 ± 6. Self-reported health status revealed an overall symptom score of 47 ± 13 on a 0-96 scale, a median POTS score of 64 (IQR 16) on a 0-120 scale, and poor measures of quality-of-life (median 25 IQR 25, on a 0-100 scale) and abilityto-work (median 0, IQR 26, on a 0-100 scale). Following 9 weeks of intermittent saline infusion (mean volume 1600 ± 360 mL), self-reported composite symptom score, quality-of-life and POTS-related symptoms improved significantly (all p<0.001), as did ability-to-work (p<0.05).

Our data derived from a non-controlled case-series indicate health benefits from volume loading with intermittent infusion of saline among patients with ME/CFS, which may stimulate further studies on various forms of intravenous volume loading to patients with ME/CFS and dysautonomia.

Source: Per Sjogren, Helena Huhmar, Bo Christer Bertilson, Björn A Bragée, Olli Polo. Beneficial effects of intermittent intravenous saline infusion in dysautonomic patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a caseseries. Front. Neurol., Sec. Autonomic Disorders, Volume 16 – 2025 | doi: 10.3389/fneur.2025.1601599 https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1601599/abstract

Core features and inherent diversity of post-acute infection syndromes

Abstract:

Post-acute infection syndromes (PAIS), i.e., long-lasting pathologies subsequent to infections that do not properly resolve, have both a common core and a broad diversity of manifestations. PAIS include a group of core symptoms (pathological fatigue, cognitive problems, sleep disorders and pain) accompanied by a large set of diverse symptoms. Core and diverse additional symptoms, which can persist for years, exhibiting periods of relapses and remissions, usually start suddenly after an apparently common infection.

PAIS display highly variable clinical features depending on the nature of the initial pathogen, and to an even larger extent, on the diversity of preexisting individual terrains in which PAIS are rooted. In a first part, I discuss biological issues related to the persistence of microbial antigens, dysregulated immune responses, reactivation of latent viruses, different potential self-sustained inflammatory loops, mitochondrial dysfunction, metabolic disorders in the tryptophan- kynurenin pathway (TKP) with impact on serotonin, and consequences of a dysfunctional bidirectional microbiota-gut-brain axis.

The second part deals with the nervous system dependence of PAIS. I rely on the concept of interoception, the process by which the brain senses, integrates and interprets signals originating from within the body, and sends feebacks aimed at maintaining homeostasis. Interoception is central for understanding the origin of fatigue, dysautonomia, dysfunctioning of the hypothalamus-pituitary-adrenal (HPA) axis, and its relation with stress, inflammation or depression.

I propose that all individual predispositions leading to self-sustained vicious circles constitute building blocks that can self-assemble in many possible ways, to give rise to both core and diverse features of PAIS. A useful discrimination between different PAIS subtypes should be obtained with a composite profiling including biomarkers, questionnaires and functional tests so as to take into account PAIS multidimensionality.

Source: Trautmann A. Core features and inherent diversity of post-acute infection syndromes. Front Immunol. 2025 Jun 3;16:1509131. doi: 10.3389/fimmu.2025.1509131. PMID: 40529374; PMCID: PMC12170329. https://pmc.ncbi.nlm.nih.gov/articles/PMC12170329/ (Full text)

Long COVID as an Infection-Associated Chronic Condition: Implications

In-Brief:

A link between infection and chronic illness has been recognized, along with the complexities of interactions between pathogen, environment, host genetics, route of exposure, and timing of outcomes. The COVID-19 pandemic has brought this issue to the forefront and Long COVID is recognized to be an infection associated chronic condition. However, given the wide range of Long COVID presentations, the singular expression gives a false sense of simplicity. Long COVID is best considered as a group of infection associated conditions requiring developing research studies and treatment trials that address the inherent heterogeneity.
Source: Unger ER. Long COVID as an Infection-Associated Chronic Condition: Implications. Am J Health Promot. 2025 Jul;39(6):960-965. doi: 10.1177/08901171241308066b. Epub 2025 Jun 8. PMID: 40485158. https://journals.sagepub.com/doi/10.1177/08901171241308066b (Full text)

Assessing the Relationship in Symptomology of Myalgic Encephalitis/Chronic Fatigue Syndrome and Long COVID

Abstract:

The symptomology of Myalgic Encephalitis/Chronic Fatigue Syndrome (ME/CFS) shares many commonalities with Long COVID (LC). This study aimed to clearly define the comparison between ME/CFS and LC in terms of symptomology.

A cross-sectional analysis of 27,651 interviewees from a National Health Interview Survey 2022 adult dataset was conducted. The data was controlled for subject’s sex, race/ethnicity, age, life satisfaction, insurance coverage, poverty ratio, and comorbidities. A logistic regression was used to compare four groups: (1) LC individuals, (2) ME/CFS individuals, (3) LC with ME/CFS individuals, and (4) controls by symptoms of depression, anxiety, physical activity, fatigue, and memory.

The results showed that subjects with both ME/CFS and LC were more likely to report memory issues, anxiety, depression, fatigue, and difficulty with physical activity followed by subjects with ME/CFS only, LC only, and the controls (P < .01).

Our study suggests a synergistic mechanism between ME/CFS and LC in developing issues with anxiety, depression, fatigue, and physically activity in patients. The study’s conclusions highlight the need to elucidate the possible overlap in pathophysiological mechanisms of ME/CFS and LC in the symptomology of patients.

Source: Garapaty N, Reyes KM, Tehrani L, Mendoza MB, Hardigan P. Assessing the Relationship in Symptomology of Myalgic Encephalitis/Chronic Fatigue Syndrome and Long COVID. Am J Med Open. 2025 Feb 1;13:100085. doi: 10.1016/j.ajmo.2024.100085. PMID: 40271015; PMCID: PMC12017839. https://pmc.ncbi.nlm.nih.gov/articles/PMC12017839/ (Full text)

Language Matters: What Not to Say to Patients with Long COVID, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and Other Complex Chronic Disorders

Abstract:

People with Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other complex chronic disorders consistently report having difficulty obtaining effective and compassionate medical care and being disbelieved, judged, gaslighted, and even dismissed by healthcare professionals. We believe that these adversarial interactions and language are more likely to arise when healthcare professionals are confronting complex chronic illnesses without proper training, diagnostic biomarkers, or FDA-approved therapies.
These problematic conversations between practitioners and patients often involve specific words and phrases—termed the “never-words”—can leave patients in significant emotional distress and negatively impact the clinician–patient relationship and recovery. Seeking to prevent these destructive interactions, we review key literature on best practices for difficult clinical conversations and discuss the application of these practices for people with Long COVID, ME/CFS, dysautonomia, and other complex chronic disorders. We provide recommendations for alternative, preferred phrasing to the never-words, which can enhance therapeutic relationship and chronic illness patient care via compassionate, encouraging, and non-judgmental language.
Source: Smyth NJ, Blitshteyn S. Language Matters: What Not to Say to Patients with Long COVID, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and Other Complex Chronic Disorders. International Journal of Environmental Research and Public Health. 2025; 22(2):275. https://doi.org/10.3390/ijerph22020275 https://www.mdpi.com/1660-4601/22/2/275 (Full text)

Long COVID and hypermobility spectrum disorders have shared pathophysiology

Abstract:

Hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) are the most common joint hypermobility conditions encountered by physicians, with hypermobile and classical EDS accounting for >90% of all cases. Hypermobility has been detected in up to 30-57% of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia, postural orthostatic tachycardia syndrome (POTS), and long COVID (LC) compared to the general population.

Extrapulmonary symptoms, including musculoskeletal pain, dysautonomia disorders, cognitive disorders, and fatigue, are seen in both LC and HSD. Additionally, ME/CFS has overlapping symptoms with those seen in HSD. Mast cell activation and degranulation occurring in both LC and ME/CFS may result in hyperinflammation and damage to connective tissue in these patients, thereby inducing hypermobility.

Persistent inflammation may result in the development or worsening of HSD. Hence, screening for hypermobility and other related conditions including fibromyalgia, POTS, ME/CFS, chronic pain conditions, joint pain, and myalgia is essential for individuals experiencing LC. Pharmacological treatments should be symptom-focused and geared to a patient’s presentation. Paced exercise, massage, yoga, and meditation may also provide benefits.

Source: Ganesh R, Munipalli B. Long COVID and hypermobility spectrum disorders have shared pathophysiology. Front Neurol. 2024 Sep 5;15:1455498. doi: 10.3389/fneur.2024.1455498. PMID: 39301475; PMCID: PMC11410636. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11410636/ (Full text)

Long COVID Is Not a Functional Neurologic Disorder

Abstract:

Long COVID is a common sequela of SARS-CoV-2 infection. Data from numerous scientific studies indicate that long COVID involves a complex interaction between pathophysiological processes. Long COVID may involve the development of new diagnosable health conditions and exacerbation of pre-existing health conditions. However, despite this rapidly accumulating body of evidence regarding the pathobiology of long COVID, psychogenic and functional interpretations of the illness presentation continue to be endorsed by some healthcare professionals, creating confusion and inappropriate diagnostic and therapeutic pathways for people living with long COVID.

The purpose of this perspective is to present a clinical and scientific rationale for why long COVID should not be considered as a functional neurologic disorder. It will begin by discussing the parallel historical development of pathobiological and psychosomatic/sociogenic diagnostic constructs arising from a common root in neurasthenia, which has resulted in the collective understandings of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and functional neurologic disorder (FND), respectively. We will also review the case definition criteria for FND and the distinguishing clinical and neuroimaging findings in FND vs. long COVID.

We conclude that considering long COVID as FND is inappropriate based on differentiating pathophysiologic mechanisms and distinguishing clinical findings.

Source: Davenport TE, Blitshteyn S, Clague-Baker N, Davies-Payne D, Treisman GJ, Tyson SF. Long COVID Is Not a Functional Neurologic Disorder. J Pers Med. 2024 Jul 29;14(8):799. doi: 10.3390/jpm14080799. PMID: 39201991. https://www.mdpi.com/2075-4426/14/8/799 (Full text)

Designing and optimizing clinical trials for long COVID

Abstract:

Long COVID is a debilitating, multisystemic illness following a SARS-CoV-2 infection whose duration may be indefinite. Over four years into the pandemic, little knowledge has been generated from clinical trials. We analyzed the information available on ClinicalTrials.gov, and found that the rigor and focus of trials vary widely, and that the majority test non-pharmacological interventions with insufficient evidence.

We highlight promising trials underway, and encourage the proliferation of clinical trials for treating Long COVID and other infection-associated chronic conditions and illnesses (IACCIs). We recommend several guidelines for Long COVID trials: First, pharmaceutical trials with potentially curative, primary interventions should be prioritized, and both drug repurposing and new drug development should be pursued.

Second, study designs should be both rigorous and accessible, e.g., triple-blinded randomized trials that can be conducted remotely, without participants needing to leave their homes.

Third, studies should have multiple illness comparator cohorts for IACCIs such as myalgic encephalomyelitis (ME/CFS) and dysautonomia, and screen for the full spectrum of symptomatology and pathologies of these illnesses.

Fourth, studies should consider inclusion/exclusion criteria with an eye towards equity and breadth of representation, including participants of all races, ethnicities, and genders most impacted by COVID-19, and including all levels of illness severity.

Fifth, involving patient-researchers in all aspects of studies brings immensely valuable perspectives that will increase the impact of trials. We also encourage the development of efficient clinical trial designs including methods to study several therapies in parallel.

Source: Vogel JM, Pollack B, Spier E, McCorkell L, Jaudon TW, Fitzgerald M, Davis H, Cohen AK. Designing and optimizing clinical trials for long COVID. Life Sci. 2024 Aug 13;355:122970. doi: 10.1016/j.lfs.2024.122970. Epub ahead of print. PMID: 39142505. https://www.sciencedirect.com/science/article/pii/S0024320524005605 (Full text)