Tag: autonomic dysfunction

Autonomic Manifestations of Long-COVID Syndrome

Abstract:

Purpose of review: Long-COVID is a novel condition emerging from the COVID-19 pandemic. Long-COVID is characterized by symptoms commonly seen in autonomic disorders including fatigue, brain fog, light-headedness, and palpitations. This article will critically evaluate recent findings and studies on Long-COVID and its physiological autonomic manifestations.

Recent findings: Studies have reported on the prevalence of different symptoms and autonomic disorders in Long-COVID cohorts. Autonomic nervous system function, including both the parasympathetic and sympathetic limbs, has been studied using different testing techniques in Long-COVID patients. While numerous mechanisms may contribute to Long-COVID autonomic pathophysiology, it is currently unclear which ones lead to a Long-COVID presentation. To date, studies have not tested treatment options for autonomic disorders in Long-COVID patients. Long-COVID is associated with autonomic abnormalities. There is a high prevalence of clinical autonomic disorders among Long-COVID patients, with limited knowledge of the underlying mechanisms and the effectiveness of treatment options.

Source: Hira R, Karalasingham K, Baker JR, Raj SR. Autonomic Manifestations of Long-COVID Syndrome. Curr Neurol Neurosci Rep. 2023 Nov 10. doi: 10.1007/s11910-023-01320-z. Epub ahead of print. PMID: 37947962. https://pubmed.ncbi.nlm.nih.gov/37947962/

High incidence of autonomic dysfunction and postural orthostatic tachycardia syndrome in patients with long-COVID: Implications for management and healthcare planning

Abstract:

Background: Autonomic dysfunction including postural orthostatic tachycardia syndrome (POTS) has been reported in individuals with post-acute sequelae of Covid-19 (PASC). However, the degree of dysautonomia in PASC has not been compared to those with POTS and healthy controls.

Methods: All participants were prospectively enrolled between 5th August 2021 and 31st October 2022. Autonomic testing included beat-to-beat hemodynamic monitoring to assess respiratory sinus arrhythmia, Valsalva ratio and orthostatic changes during a 10-minute active standing test as well as Sudomotor assessment. The Composite Autonomic Symptom Score (COMPASS-31) was used to assess symptoms and the Euroquol 5-Dimension survey (EQ-5D-5L) was used to assess health-related quality of life (HrQoL) measures.

Results: A total of 99 participants (n=33 PASC, n=33 POTS and n=33 healthy controls; median age 32 [18], 85.9% females) were included. Compared to healthy controls, the PASC and POTS cohorts demonstrated significantly reduced respiratory sinus arrhythmia (p<0.001), greater heart rate increase during 10-minute active standing test (p<0.001), greater burden of autonomic dysfunction evidenced by higher COMPASS-31 scores across all subdomains (all p<0.001) and poor HrQoL across all EQ-5D-5L domains (all p<0.001), lower median EQ-VAS (p<0.001) and lower utility scores (p<0.001). The majority (79%) of those with PASC met the internationally established criteria for POTS.

Conclusion: The prevalence of autonomic symptomology or POTS was high in those with PASC, leading to poor HrQoL and high health disutility. Autonomic testing should be routinely undertaken in those with PASC to aid diagnosis and direct appropriate management to improve health outcomes.

Trial registration: ANZCTR 12621000476831.

Source: Seeley MC, Gallagher C, Ong E, Langdon A, Chieng J, Bailey D, Page A, Lim HS, Lau DH. High incidence of autonomic dysfunction and postural orthostatic tachycardia syndrome in patients with long-COVID: Implications for management and healthcare planning. Am J Med. 2023 Jun 28:S0002-9343(23)00402-3. doi: 10.1016/j.amjmed.2023.06.010. Epub ahead of print. PMID: 37391116. https://www.amjmed.com/article/S0002-9343(23)00402-3/fulltext (Full text)

Converging Evidence of Similar Symptomatology of ME/CFS and PASC Indicating Multisystemic Dyshomeostasis

Abstract:

The purpose of this article is to review the evidence of similar symptomatology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-acute sequelae of SARS-CoV-2 infection (PASC).
Reanalysis of data from a study by Jason comparing symptom reports from two groups of ME/CFS and PASC patients shows a notably similar symptomatology. Symptom scores of the PASC group and the ME/CFS group correlated 0.902 (p < 0.0001) across items. The hypothesis is presented that ME/CFS and PASC are caused by a chronic state of multisystemic disequilibrium including endocrinological, immunological, and/or metabolic changes.
The hypothesis holds that a changed set point persistently pushes the organism towards a pathological dysfunctional state which fails to reset. To use an analogy of a thermostat, if the ‘off switch’ of a thermostat intermittently stops working, for periods the house would become warmer and warmer without limit. The hypothesis draws on recent investigations of the Central Homeostasis Network showing multiple interconnections between the autonomic system, central nervous system, and brain stem.
The hypothesis helps to explain the shared symptomatology of ME/CFS and PASC and the unpredictable, intermittent, and fluctuating pattern of symptoms of ME/CFS and PASC. The current theoretical approach remains speculative and requires in-depth investigation before any definite conclusions can be drawn.
Source: Marks DF. Converging Evidence of Similar Symptomatology of ME/CFS and PASC Indicating Multisystemic Dyshomeostasis. Biomedicines. 2023; 11(1):180. https://doi.org/10.3390/biomedicines11010180 https://www.mdpi.com/2227-9059/11/1/180 (Full text)

Blunted short-term autonomic cardiovascular reactivity to orthostatic and clinostatic challenges in fibromyalgia as an indicator of the severity of chronic pain

Abstract:

Fibromyalgia is a long-term pain disorder that has been related to autonomic dysfunctions and reduced cardiovascular reactivity. We aimed to assess the dynamic short-term cardiovascular responses to postural changes in fibromyalgia. Thirty-eight women with fibromyalgia and thirty-six healthy women underwent the “Chronic Pain Autonomic Stress Test”.

Electrocardiogram, blood pressure and impedance cardiography were continuously recorded during active standing and lying down. Second-by-second values were derived over the first 30 s of each posture. Lower reactivity during the beginning of each position was observed in fibromyalgia sufferers compared to healthy women, with smaller responses seen during stand up in heart rate, blood pressure, cardiac output, total peripheral resistance, and pre-ejection period, and smaller changes during lying down in heart rate, cardiac output and total peripheral resistance. The magnitude of the autonomic adjustments to postural changes was inversely associated with the severity of clinical pain.

These findings indicate an early impaired autonomic cardiovascular response to orthostatic and clinostatic challenges in fibromyalgia, suggesting less autonomic flexibility and adaptability to situational demands and challenges. Short-term second-by-second cardiovascular measures may be useful in the clinical assessment of fibromyalgia.

Source: Contreras-Merino AM, Davydov DM, Galvez-Sánchez CM, Reyes Del Paso GA. Blunted short-term autonomic cardiovascular reactivity to orthostatic and clinostatic challenges in fibromyalgia as an indicator of the severity of chronic pain. Int J Psychophysiol. 2022 May;175:61-70. doi: 10.1016/j.ijpsycho.2022.03.001. Epub 2022 Mar 11. PMID: 35283267. https://www.sciencedirect.com/science/article/pii/S0167876022000599?via%3Dihub (Full text)

Network autonomic analysis of post-acute sequelae of COVID-19 and postural tachycardia syndrome

Abstract:

Background: The autonomic nervous system (ANS) is a complex network where sympathetic and parasympathetic domains interact inside and outside of the network. Correlation-based network analysis (NA) is a novel approach enabling the quantification of these interactions. The aim of this study is to assess the applicability of NA to assess relationships between autonomic, sensory, respiratory, cerebrovascular, and inflammatory markers on post-acute sequela of COVID-19 (PASC) and postural tachycardia syndrome (POTS).

Methods: In this retrospective study, datasets from PASC (n = 15), POTS (n = 15), and matched controls (n = 11) were analyzed. Networks were constructed from surveys (autonomic and sensory), autonomic tests (deep breathing, Valsalva maneuver, tilt, and sudomotor test) results using heart rate, blood pressure, cerebral blood flow velocity (CBFv), capnography, skin biopsies for assessment of small fiber neuropathy (SFN), and various inflammatory markers. Networks were characterized by clusters and centrality metrics.

Results: Standard analysis showed widespread abnormalities including reduced orthostatic CBFv in 100%/88% (PASC/POTS), SFN 77%/88%, mild-to-moderate dysautonomia 100%/100%, hypocapnia 87%/100%, and elevated inflammatory markers. NA showed different signatures for both disorders with centrality metrics of vascular and inflammatory variables playing prominent roles in differentiating PASC from POTS.

Conclusions: NA is suitable for a relationship analysis between autonomic and nonautonomic components. Our preliminary analyses indicate that NA can expand the value of autonomic testing and provide new insight into the functioning of the ANS and related systems in complex disease processes such as PASC and POTS.

Source: Novak P, Giannetti MP, Weller E, Hamilton MJ, Mukerji SS, Alabsi HS, Systrom D, Marciano SP, Felsenstein D, Mullally WJ, Pilgrim DM, Castells M. Network autonomic analysis of post-acute sequelae of COVID-19 and postural tachycardia syndrome. Neurol Sci. 2022 Sep 28:1–12. doi: 10.1007/s10072-022-06423-y. Epub ahead of print. PMID: 36169757; PMCID: PMC9517969. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9517969/ (Full text)

Post-COVID-19 Syndrome: A Novel Diagnosis

Abstract:

Patients with post-COVID-19 syndrome have reported a wide array of symptoms that include autonomic dysfunction. It is hypothesized that this may be secondary to interruption of baroreflex pathways in the carotid arteries or nucleus tractus solitarius, however, confirming studies have yet to be performed. A limited number of studies have highlighted the presence of an exaggerated baroreflex response in patients with a post-COVID-19 syndrome that mirror other chronic autonomic dysfunction-related conditions.

Source: Kalia R, Kalia R, Musih J, Cubelo M, Popat J. Post-COVID-19 Syndrome: A Novel Diagnosis. Cureus. 2022 Aug 22;14(8):e28266. doi: 10.7759/cureus.28266. PMID: 36158335; PMCID: PMC9491485. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491485/ (Full text)

Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Some patients with acute COVID-19 are left with persistent, debilitating fatigue, cognitive impairment (“brain fog”), orthostatic intolerance (OI) and other symptoms (“Long COVID”). Many of the symptoms are like those of other post-infectious fatigue syndromes and may meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Common diagnostic laboratory tests are often unrevealing.

Methods: We evaluated whether a simple, standardized, office-based test of OI, the 10-min NASA Lean Test (NLT), would aggravate symptoms and produce objective hemodynamic and cognitive abnormalities, the latter being evaluated by a simple smart phone-based app.

Participants: People with Long COVID (N = 42), ME/CFS (N = 26) and healthy control subjects (N = 20) were studied just before, during, immediately after, 2 and 7 days following completion of the NLT.

Results: The NLT provoked a worsening of symptoms in the two patient groups but not in healthy control subjects, and the severity of all symptoms was similar and significantly worse in the two patient groups than in the control subjects (p < 0.001). In the two patient groups, particularly those with Long COVID, the NLT provoked a marked and progressive narrowing in the pulse pressure. All three cognitive measures of reaction time worsened in the two patient groups immediately following the NLT, compared to the healthy control subjects, particularly in the Procedural Reaction Time (p < 0.01).

Conclusions: A test of orthostatic stress easily performed in an office setting reveals different symptomatic, hemodynamic and cognitive abnormalities in people with Long COVID and ME/CFS, compared to healthy control subjects. Thus, an orthostatic challenge easily performed in an office setting, and the use of a smart phone app to assess cognition, can provide objective confirmation of the orthostatic intolerance and brain fog reported by patients with Long COVID and ME/CFS.

Source: Vernon SD, Funk S, Bateman L, Stoddard GJ, Hammer S, Sullivan K, Bell J, Abbaszadeh S, Lipkin WI, Komaroff AL. Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Med (Lausanne). 2022 Jun 23;9:917019. doi: 10.3389/fmed.2022.917019. PMID: 35847821; PMCID: PMC9285104. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285104/ (Full text)

Impaired Cardiac Autonomic Control in Women With Fibromyalgia Is Independent of Their Physical Fitness

Abstract:

Background/objective: Evidence has suggested abnormal cardiac autonomic responses to exercise in patients with fibromyalgia (FM). However, it is not clear whether the dysautonomia represents a reduced physical fitness rather directly related to FM pathogenesis. Thus, we aimed to verify the cardiac autonomic responses before, during, and after a maximal incremental exercise in women with FM and whether these hypothesized alterations would be dependent with their physical fitness.

Methods: This is a cross-sectional study with 23 FM women and 17 healthy women. The participants performed a maximal incremental cycling test to determine their maximal workload (Wmax) and were further matched by their Wmax (14 FM patients, Wmax: 128.6 ± 16.2 W; and 14 healthy women, Wmax: 131.9 ± 15.9 W). Beat-to-beat heart rate (HR) was continuously monitored to calculate HR variability indexes at rest, chronotropic reserve during exercise, and HR recovery.

Results: Heart rate variability indexes related to vagal modulation were significantly lower in FM patients than in healthy women (p < 0.05). The chronotropic reserve and the HR recovery at 30, 120, 180, 300, and 600 seconds after exercise were all lower in FM patients compared with those of healthy women (p < 0.05). Similar findings were found when analysis was performed using the matched physical fitness subgroup.

Conclusions: The documented cardiac autonomic abnormalities at rest, during, and after exercise in FM patients persist even when physical fitness status is taken in account. Thus, strategies to attenuate the dysautonomia in FM patients must be considered.

Source: Schamne JC, Ressetti JC, Lima-Silva AE, Okuno NM. Impaired Cardiac Autonomic Control in Women With Fibromyalgia Is Independent of Their Physical Fitness. J Clin Rheumatol. 2021 Sep 1;27(6S):S278-S283. doi: 10.1097/RHU.0000000000001518. PMID: 32826659. https://pubmed.ncbi.nlm.nih.gov/32826659/

Preparing for the long-haul: Autonomic complications of COVID-19

Abstract:

As global numbers of COVID-19 grow, chronic neurological symptoms, including those of autonomic dysfunction, are being reported with increasing frequency. Mounting evidence suggests that many patients experience chronic and sometimes debilitating symptoms long after their acute infectious period, leading to the new diagnostic category of post-acute COVID syndrome. Many symptoms of post-acute COVID syndrome appear autonomic in nature, suggesting that autonomic impairment may play a central role in the underlying pathophysiology. In this review, we discuss the autonomic symptoms and manifestations of post-acute COVID syndrome, potential mechanisms involved, and future directions for a better understanding of this novel condition.

Source: Larsen NW, Stiles LE, Miglis MG. Preparing for the long-haul: Autonomic complications of COVID-19. Auton Neurosci. 2021;235:102841. doi:10.1016/j.autneu.2021.102841  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254396/ (Full text)

Long COVID and the Autonomic Nervous System: The Journey from Dysautonomia to Therapeutic Neuro-Modulation through the Retrospective Analysis of 152 Patients

Abstract:

Introduction. The severity and prevalence of Post-Acute COVID-19 Sequela (PACS) or long-COVID syndrome (long COVID) should not be a surprise. Long-COVID symptoms may be explained by oxidative stress and parasympathetic and sympathetic (P&S) dysfunction. This is a retrospective, hypothesis generating, outcomes study.
Methods. From two suburban practices in northeastern United States, 152 long COVID patients were exposed to the following practices: (1) first, they were P&S tested (P&S Monitor 4.0; Physio PS, Inc., Atlanta, GA, USA) prior to being infected with COVID-19 due to other causes of autonomic dysfunction; (2) received a pre-COVID-19 follow-up P&S test after autonomic therapy; (3) then, they were infected with COVID-19; (4) P&S tested within three months of surviving the COVID-19 infection with long-COVID symptoms; and, finally, (5) post-COVID-19, follow-up P&S tested, again, after autonomic therapy. All the patients completed autonomic questionnaires with each test. This cohort included 88 females (57.8%), with an average age of 47.0 years (ranging from 14 to 79 years), and an average BMI of 26.9 #/in2. Results. More pre-COVID-19 patients presented with sympathetic withdrawal than parasympathetic excess. Post-COVID-19, these patients presented with this ratio reversed and, on average, 49.9% more autonomic symptoms than they did pre-COVID-19.
Discussion. Both parasympathetic excess and sympathetic withdrawal are separate and treatable autonomic dysfunctions and autonomic treatment significantly reduces the prevalence of autonomic symptoms.
Conclusion. SARS-CoV-2, via its oxidative stress, can lead to P&S dysfunction, which, in turn, affects the control and coordination of all systems throughout the whole body and may explain all of the symptoms of long-COVID syndrome. Autonomic therapy leads to positive outcomes and patient quality of life may be restored.
Source: Colombo J, Weintraub MI, Munoz R, Verma A, Ahmad G, Kaczmarski K, Santos L, DePace NL. Long COVID and the Autonomic Nervous System: The Journey from Dysautonomia to Therapeutic Neuro-Modulation through the Retrospective Analysis of 152 Patients. NeuroSci. 2022; 3(2):300-310. https://doi.org/10.3390/neurosci3020021 https://www.mdpi.com/2673-4087/3/2/21/htm (Full text)