Tag: dysautonomia

Complex syndromes of chronic pain, fatigue and cognitive impairment linked to autoimmune dysautonomia and small fiber neuropathy

Abstract:

Chronic fatigue syndrome, postural orthostatic tachycardia syndrome, complex regional pain syndrome and silicone implant incompatibility syndrome are a subject of debate among clinicians and researchers. Both the pathogenesis and treatment of these disorders require further study.

In this paper we summarize the evidence regarding the role of autoimmunity in these four syndromes with respect to immunogenetics, autoimmune co-morbidities, alteration in immune cell subsets, production of autoantibodies and presentation in animal models. These syndromes could be incorporated in a new concept of autoimmune neurosensory dysautonomia with the common denominators of autoantibodies against G-protein coupled receptors and small fiber neuropathy.

Sjogren’s syndrome, which is a classical autoimmune disease, could serve as a diseases model, illustrating the concept. Development of this concept aims to identify an apparently autoimmune subgroup of the disputable disorders, addressed in the review, which may mostly benefit from the immunotherapy.

Copyright © 2020. Published by Elsevier Inc.

Source: Shoenfeld Y, Ryabkova VA, Sheibenbogen C, Brinth L, Martinez-Lavin M, Ikeda S, Heidecke H, Watad A, Bragazzi NL, Chapman J, Churilov LP, Amital H. Complex syndromes of chronic pain, fatigue and cognitive impairment linked to autoimmune dysautonomia and small fiber neuropathy. Clin Immunol. 2020 Mar 11:108384. doi: 10.1016/j.clim.2020.108384. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32171889

Network structure underpinning (dys)homeostasis in chronic fatigue syndrome; Preliminary findings

Abstract:

INTRODUCTION: A large body of evidence has established a pattern of altered functioning in the immune system, autonomic nervous system and hypothalamic pituitary adrenal axis in chronic fatigue syndrome. However, the relationship between components within and between these systems is unclear. In this paper we investigated the underlying network structure of the autonomic system in patients and controls, and a larger network comprising all three systems in patients alone.

METHODS: In a sample of patients and controls we took several measures of autonomic nervous system output during 10 minutes of supine rest covering tests of blood pressure variability, heart rate variability and cardiac output. Awakening salivary cortisol was measured on each of two days with participants receiving 0.5mg dexamethasone during the afternoon of the first day. Basal plasma cytokine levels and the in vitro cytokine response to dexamethasone were also measured. Symptom outcome measures used were the fatigue impact scale and cognitive failures questionnaire. Mutual information criteria were used to construct networks describing the dependency amongst variables. Data from 42 patients and 9 controls were used in constructing autonomic networks, and 15 patients in constructing the combined network.

RESULTS: The autonomic network in patients showed a more uneven distribution of information, with two distinct modules emerging dominated by systolic blood pressure during active stand and end diastolic volume and stroke volume respectively. The combined network revealed strong links between elements of each of the three regulatory systems, characterised by three higher modules the centres of which were systolic blood pressure during active stand, stroke volume and ejection fraction respectively.

CONCLUSIONS: CFS is a complex condition affecting physiological systems. It is important that novel analytical techniques are used to understand the abnormalities that lead to CFS. The underlying network structure of the autonomic system is significantly different to that of controls, with a small number of individual nodes being highly influential. The combined network suggests links across regulatory systems which shows how alterations in single nodes might spread throughout the network to produce alterations in other, even distant, nodes. Replication in a larger cohort is warranted.

Source: Clark JE, Ng WF, Rushton S, Watson S, Newton JL. Network structure underpinning (dys)homeostasis in chronic fatigue syndrome; Preliminary findings. PLoS One. 2019 Mar 25;14(3):e0213724. doi: 10.1371/journal.pone.0213724. eCollection 2019. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213724 (Full article)

The effects of warm water immersion on blood pressure, heart rate and heart rate variability in people with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a central sensitisation syndrome with abnormalities in autonomic regulation of blood pressure (BP), heart rate (HR) and heart rate variability (HRV). Prior to exploring the effects of hydrotherapy as a treatment for this population, changes in BP, HR and HRV during warm water immersion need to be established.

OBJECTIVES: The study aimed to determine the effects of warm water immersion on BP, HR and HRV in adults with CFS compared to matched-pair healthy adults.

METHOD: A quasi-experimental, single-blinded study design was used with nine CFS participants and nine matched controls. Participants’ BP, HR and HRV were measured before, after 5 minutes and post warm water immersion at the depth of the fourth intercostal space, using the Ithlete® System and Dräger BP monitor.

RESULTS: There was a significant difference between groups in HRV prior to immersion (control group: 73 [55-74] vs. chronic fatigue syndrome group: 63 [50-70]; p = 0.04). There was no difference in HRV post-immersion. A significant difference in HR after immersion was recorded with the control group having a lower HR than those with CFS (78 [60-86] vs. 86 [65-112]; p = 0.03). The low HRV present in the CFS group prior to immersion suggests autonomic dysregulation. Individuals with CFS may have reduced vagal nerve activation post-immersion. During immersion, HRV of the CFS participants improved similar to that of the healthy controls.

CONCLUSION: Prior to immersion, differences were present in the HRV of the participants with CFS compared to healthy controls. These differences were no longer present post-immersion.

CLINICAL IMPLICATIONS: Warm water immersion appears safe and may be beneficial in the management of individuals with CFS.

Source: Parker R, Higgins Z, Mlombile ZNP, Mohr MJ, Wagner TL. The effects of warm water immersion on blood pressure, heart rate and heart rate variability in people with chronic fatigue syndrome. S Afr J Physiother. 2018 Aug 28;74(1):442. doi: 10.4102/sajp.v74i1.442. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131699/ (Full article)

Cardiac sympathetic innervation associates with autonomic dysfunction in chronic fatigue syndrome – a pilot study

Despite hemodynamic abnormalities being well documented in chronic fatigue syndrome (CFS), it remains unclear the nature of the underlying autonomic nervous system problems that underpin these findings. Studies performed in subgroups of those with CFS suggest cardiac sympathetic denervation.

Meta-iodo-benzylguanidine (MIBG) imaging provides a quantitative measure of cardiac sympathetic innervation. Clinically, cardiac MIBG scanning is used to estimate local myocardial sympathetic nerve damage in heart disease and dysautonomia, particularly abnormalities arising due to sympathetic innervation [1,2]. In this study, we explored potential mechanisms that underpin the autonomic abnormalities seen in CFS using I125 MIBG participants that fulfilled Fukuda diagnostic criteria for CFS [3]. Participants were excluded if screened positive for a major depressive episode (Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders). Fatigue was measured using the Fatigue Impact Scale (FIS).

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Source: Petrides G, Zalewski P, McCulloch D, Maclachlan L, Finkelmeyer A, Hodgson T, Blamire A, Newton JL. Cardiac sympathetic innervation associates with autonomic dysfunction in chronic fatigue syndrome – a pilot study. Fatigue. 2017 May 4;5(3):184-186. doi: 10.1080/21641846.2017.1322235. eCollection 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5942146/ (Full article)

Autonomic Nervous System Functioning Related to Nocturnal Sleep in Patients With Chronic Fatigue Syndrome Compared to Tired Controls

Abstract:

STUDY OBJECTIVES: Autonomic nervous system (ANS) dysfunction is common in chronic fatigue syndrome (CFS). One of the main complaints in CFS is unrefreshing sleep. We aimed to study the nocturnal cardiac ANS in different sleep stages in patients filling the 2015 Institute of Medicine CFS diagnostic criteria.

METHODS: In this case series study, the nocturnal heart rate variability and blood pressure (BP) variables in polysomnography were studied in groups of patients with CFS (n = 8) and tired controls (n = 8) aged 16-49 years. Five of the patients with CFS and controls were female. The heart rate variability and BP parameters and heart rate were studied in all sleep stages and wake.

RESULTS: The amount of low-frequency oscillations of the electrocardiography R-R-intervals spectra (LF; predominantly reflects sympathetic activity) was higher for patients with CFS in all sleep stages compared to controls (P< .001). During wake, the amount of LF was lower for the patients with CFS (P< .05). The amount of high-frequency oscillations (HF; reflects parasympathetic activity) was lower in stage N3 sleep in the patients with CFS than for the controls (P< .0001), but, in total, HF was higher in patients with CFS (P< .001). Patients with CFS had higher overall nocturnal systolic and mean BP (P< .0001) and lower heart rate (P< .0001) than controls. No significant differences were found in sleep stage distributions.

CONCLUSIONS: The results suggest a nocturnal dysfunction of the cardiac ANS in CFS, presenting as lower parasympathetic tone in deep sleep and higher sympathetic tone asleep.

Source: Orjatsalo M, Alakuijala A, Partinen M. Autonomic Nervous System Functioning Related to Nocturnal Sleep in Patients With Chronic Fatigue Syndrome Compared to Tired Controls. J Clin Sleep Med. 2017 Dec 13. pii: jc-17-00330. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29246267

Sympathetic nervous system dysfunction in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis: a review of case-control studies

Abstract:

BACKGROUND: Fibromyalgia often coexists and overlaps with other syndromes such as chronic fatigue, irritable bowel syndrome, and interstitial cystitis. Chronic stress has been implicated in the pathogenesis of these illnesses. The sympathetic nervous system is a key element of the stress response system. Sympathetic dysfunction has been reported in these syndromes, raising the possibility that such dysautonomia could be their common clustering underlying pathogenesis.

OBJECTIVE: The objective of this study was to carry out a review of all published comparative case-control studies investigating sympathetic nervous system performance in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis.

METHODS: Online databases PubMed and EMBASE were accessed using the following key words: autonomic (OR) sympathetic (AND) fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis. All entries up to December 10th 2012 were reviewed by 2 independent investigators searching for case-control studies in humans. The Method for Evaluating Research and Guidelines Evidence adapted to the Scottish Intercollegiate Guidelines Network was used to rank the level of evidence contained in the selected articles.

RESULTS: A total of 196 articles are included in this review. The most often used methods to assess sympathetic functionality were heart rate variability analysis, sympathetic skin response, tilt table testing, and genetic studies. The majority of studies (65%) described sympathetic nervous system predominance in these overlapping syndromes. In contrast, 7% of the studies found parasympathetic predominance.

CONCLUSIONS: This review demonstrates that sympathetic nervous system predominance is common in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis. This concordance raises the possibility that sympathetic dysfunction could be their common underlying pathogenesis that brings on overlapping clinical features. The recognition of sympathetic predominance in these 4 syndromes may have potential clinical implications. It may be worth exploring the use of nonpharmacological measures as well as drug therapies aimed to regain autonomic balance.

 

Source: Martínez-Martínez LA, Mora T, Vargas A, Fuentes-Iniestra M, Martínez-Lavín M. Sympathetic nervous system dysfunction in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis: a review of case-control studies. J Clin Rheumatol. 2014 Apr;20(3):146-50. doi: 10.1097/RHU.0000000000000089. https://www.ncbi.nlm.nih.gov/pubmed/24662556

 

Adolescent chronic fatigue syndrome; a follow-up study displays concurrent improvement of circulatory abnormalities and clinical symptoms

Abstract:

BACKGROUND: The pathophysiology of chronic fatigue syndrome (CFS) in adolescents is unknown, and the clinical course and prognosis is still questioned. Recent research indicates that abnormalities of autonomic cardiovascular control may play an important role. The aim of this research project was to perform a follow-up study of adolescents with chronic fatigue syndrome, focusing on clinical symptoms and autonomic cardiovascular control.

METHODS: 47 adolescents (12-18 years old) with CFS were recruited from the outpatient clinic at the Department of Pediatrics, Oslo University Hospital. In a primary visit and a follow-up visit (3-17 months later), we evaluated: a) a wide range of complaints and symptoms and b) cardiovascular variables at baseline and during a 20° head-up tilt-test (HUT).

RESULTS: At the second visit, patients reported significant improvement regarding functional impairments, fatigue severity, muscular pain, concentration problems, post-exertional malaise and the problem of non-relieving rest. Also, at the second visit, baseline heart rate (HR), blood pressure, total peripheral resistance index (TPRI) and LF/HF (low-frequency:high-frequency heart rate variability ratio, an index of sinus node sympathovagal balance derived from spectral analyses of heart rate) were significant lower, and the increases in HR, mean blood pressure (MBP), diastolic blood pressure (DBP) and TPRI during tilt were significantly less pronounced as compared to the first visit. There was a significant correlation between changes in autonomic symptom score, fatigue severity score and functional impairment score from the first to the second visit.

CONCLUSIONS: The majority of adolescents with CFS experienced an improvement over time in functional impairment, self-reported fatigue and additional symptoms, and a concurrent improvement of autonomic cardiovascular control. A possible connection between clinical symptoms and abnormal autonomic control in CFS might represent a focus for further research.

 

Source: Sulheim D, Hurum H, Helland IB, Thaulow E, Wyller VB. Adolescent chronic fatigue syndrome; a follow-up study displays concurrent improvement of circulatory abnormalities and clinical symptoms. Biopsychosoc Med. 2012 Mar 21;6:10. doi: 10.1186/1751-0759-6-10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337799/ (Full article)

 

Cervical neuro-muscular syndrome: discovery of a new disease group caused by abnormalities in the cervical muscles

Abstract:

Our previous study of whiplash injury found that abnormalities in the cervical muscles cause autonomic dystonia. Further research has found that abnormalities in the cervical muscles cause headache, chronic fatigue syndrome, vertigo, and dizziness. We named this group of diseases cervical neuro-muscular syndrome. Patients treated within a 2-year period from April 1, 2002 to March 31, 2004 reported good outcomes in 83.8% for headache, 88.4% for vertigo and dizziness, 84.5% for chronic fatigue syndrome, 88.0% for autonomic dystonia, and 83.7% for whiplash-associated disorder. A large number of outpatients present with general malaise, including many general physical complaints without identifiable cause. We propose that treatment of the cervical muscle is effective for general malaise.

 

Source: Matsui T, Ii K, Hojo S, Sano K. Cervical neuro-muscular syndrome: discovery of a new disease group caused by abnormalities in the cervical muscles. Neurol Med Chir (Tokyo). 2012;52(2):75-80. https://www.jstage.jst.go.jp/article/nmc/52/2/52_2_75/_pdf (Full article)

 

Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis–a new potential diagnostic biomarker

Abstract:

Autonomic nervous system dysfunction is frequently reported in chronic fatigue syndrome (CFS) with orthostatic intolerance, a common symptom that can be objectively assessed. The frequent finding of autonomic dysfunction and symptoms on standing has the potential to provide a diagnostic biomarker in chronic fatigue. In this study we explored the clinical value of non-invasive optical multi-site photoplethysmography (PPG) technology to assess cardiovascular responses to standing.

Multi-site PPG pulses were collected from tissue pads of the ears, fingers and toes of 14 patients with CFS and 14 age-matched sedentary subjects using a measurement protocol of a 10 min baseline (subject supine) followed by 3 min of tilting on a tilt table (head-up to 70°). Percentage change in pulse timing (pulse transit time, PTTf) and pulse amplitude (AMP) at each site were calculated using beat-to-beat pulse wave analysis.

A significant reduction in the overall pulse timing response to controlled standing was found for the CFS group (using summed absolute percentage change in PTTf for ear, finger and toe sites, median change of 26% for CFS and 37% for control with p = 0.002).

There were no significant differences between subject groups for the AMP measure at any site. Changes in AMP with tilt were, however, weakly significantly and negatively correlated with fatigue severity (p < 0.05). Receiver operating characteristic (ROC) analysis of timing measures produced an area under the curve of 0.81. Experimental linear discriminant classification analysis comparing both timing and amplitude measures produced an overall diagnostic accuracy of 82%.

Pulse wave abnormalities have been observed in CFS and represent a potential objective measure to help differentiate between CFS patients and healthy controls.

 

Source: Allen J, Murray A, Di Maria C, Newton JL. Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis–a new potential diagnostic biomarker. Physiol Meas. 2012 Feb;33(2):231-41. doi: 10.1088/0967-3334/33/2/231. Epub 2012 Jan 25. https://www.ncbi.nlm.nih.gov/pubmed/22273713

 

Orthostatic symptoms predict functional capacity in chronic fatigue syndrome: implications for management

Abstract:

OBJECTIVES: To establish the relationship between the functional impairment experienced by Chronic fatigue syndrome (CFS) patients and the symptoms frequently experienced by those with CFS; specifically cognitive impairment, fatigue and orthostatic symptoms.

DESIGN: Cross sectional questionnaire survey.

SETTING: Specialist CFS Clinical Service.

SUBJECTS: Ninety-nine Fukuda diagnosed CFS and 64-matched controls.

MAIN OUTCOME MEASURES: Symptom and functional assessment tools completed and returned by post included; PROMIS HAQ (Patient-Reported Outcomes Measurement Information System, Health Assessment Questionnaire), CFQ (Cognitive Failures Questionnaire), FIS (Fatigue Impact Scale) and OGS (Orthostatic Grading Scale) assessment tools.

RESULTS: CFS patients experience greater functional impairment than controls [mean (95% CI) PROMIS HAQ scores CFS 36 (31-42) vs. controls 6 (2-10); P < 0.0001], especially in the functional domains of activities and reach. Poorer functional ability impairment is significantly associated with greater cognitive impairment (P = 0.0002, r = 0.4), fatigue (P < 0.0001, r = 0.5) and orthostatic symptoms (P < 0.0001, r = 0.6). However, only orthostatic symptoms (OGS) independently associated with functional impairment (beta = 0.4, P = 0.01).

CONCLUSION: Treatment of orthostatic symptoms in CFS has the potential to improve functional capacity and so improve quality of life.

 

Source: Costigan A, Elliott C, McDonald C, Newton JL. Orthostatic symptoms predict functional capacity in chronic fatigue syndrome: implications for management. QJM. 2010 Aug;103(8):589-95. doi: 10.1093/qjmed/hcq094. Epub 2010 Jun 9. http://qjmed.oxfordjournals.org/content/103/8/589.long (Full article)