Tag: dysautonomia

Dysautonomia and small fiber neuropathy in post-COVID condition and Chronic Fatigue Syndrome

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID condition can present similarities such as fatigue, brain fog, autonomic and neuropathic symptoms.

Methods: The study included 87 patients with post-COVID condition, 50 patients with ME/CFS, and 50 HC. The hemodynamic autonomic function was evaluated using the deep breathing technique, Valsalva maneuver, and Tilt test. The presence of autonomic and sensory small fiber neuropathy (SFN) was assessed with the Sudoscan and with heat and cold evoked potentials, respectively. Finally, a complete neuropsychological evaluation was performed. The objective of this study was to analyze and compare the autonomic and neuropathic symptoms in post-COVID condition with ME/CFS, and healthy controls (HC), as well as, analyze the relationship of these symptoms with cognition and fatigue.

Results: Statistically significant differences were found between groups in heart rate, with ME/CFS group presenting the highest (H = 18.3; p ≤ .001). The Postural Orthostatic Tachycardia Syndrome (POTS), and pathological values in palms on the Sudoscan were found in 31% and 34% of ME/CFS, and 13.8% and 19.5% of post-COVID patients, respectively. Concerning evoked potentials, statistically significant differences were found in response latency to heat stimuli between groups (H = 23.6; p ≤ .01). Latency was highest in ME/CFS, and lowest in HC. Regarding cognition, lower parasympathetic activation was associated with worse cognitive performance.

Conclusions: Both syndromes were characterized by inappropriate tachycardia at rest, with a high percentage of patients with POTS. The prolonged latencies for heat stimuli suggested damage to unmyelinated fibers. The higher proportion of patients with pathological results for upper extremities on the Sudoscan suggested a non-length-dependent SFN.

Source: Naiara Azcue, Rocio Del Pino, Marian Acera et al. Dysautonomia and small fiber neuropathy in post-COVID condition and Chronic Fatigue Syndrome, 06 October 2023, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3388628/v1] https://www.researchsquare.com/article/rs-3388628/v1 (Full text)

Prevalence, pathogenesis and spectrum of neurological symptoms in COVID-19 and post-COVID-19 syndrome: a narrative review

Summary:

  • Neurological symptoms are not uncommon during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and reflect a broad spectrum of neurological disorders of which clinicians should be aware.
  • The underlying pathogenesis of neurological disease in coronavirus disease 2019 (COVID-19) may be due to four mechanisms of nervous system dysfunction and injury: i) direct viral neurological invasion; ii) immune dysregulation; iii) endothelial dysfunction and coagulopathy; and iv) severe systemic COVID-19 disease.
  • Neurological manifestations of acute COVID-19 include headache, peripheral neuropathies, seizures, encephalitis, Guillain–Barré syndrome, and cerebrovascular disease.
  • Commonly reported long term neurological sequelae of COVID-19 are cognitive dysfunction and dysautonomia, which despite being associated with severe acute disease are also seen in people with mild disease.
  • Assessment of cognitive dysfunction after COVID-19 is confounded by a high prevalence of comorbid fatigue, anxiety, and mood disorders. However, other markers of neuroaxonal breakdown suggest no significant neuronal injury apart from during severe acute COVID-19.
  • The long term impact of COVID-19 on neurological diseases remains uncertain and requires ongoing vigilance.

Source: Wesselingh, R. (2023), Prevalence, pathogenesis and spectrum of neurological symptoms in COVID-19 and post-COVID-19 syndrome: a narrative review. Med J Aust. https://doi.org/10.5694/mja2.52063 https://onlinelibrary.wiley.com/doi/10.5694/mja2.52063 (Full text available as PDF file)

 

Increased gut permeability and bacterial translocation are associated with fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome: implications for disease-related biomarker discovery

Abstract:

Background: There is growing evidence of the significance of gastrointestinal complaints in the impairment of the intestinal mucosal barrier function and inflammation in fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome. However, data on intestinal permeability and gut barrier dysfunction in FM and ME/CFS are still limited with conflicting results. This study aimed to assess circulating biomarkers potentially related to intestinal barrier dysfunction and bacterial translocation and their association with self-reported symptoms in these conditions.

Methods: A pilot multicentre, cross-sectional cohort study with consecutive enrolment of 22 patients with FM, 30 with ME/CFS, and 26 matched healthy controls. Plasma levels of anti-beta-lactoglobulin antibodies (IgG anti-beta-LGB), zonulin-1 (ZO-1), LPS, sCD14, and IL-1β) were assayed using ELISA. Demographic and clinical characteristics of the participants were recorded using validated self-reported outcome measures. The diagnostic accuracy of each biomarker was assessed using the ROC curve analysis.

Results: FM patients had significantly higher levels of anti-β-LGB, ZO-1, LPS, and sCD14 than healthy controls (all P < 0.0001). In ME/CFS patients, levels of anti-β-LGB, ZO-1, LPS, and sCD14 were significantly higher than controls, but lower than in FM (all P < 0.01), while there was no significant difference in IL-1β level. In the FM and ME/CFS cohorts, both anti-β-LGB and ZO-1 correlated significantly with LPS and sCD14 (P < 0.001 for both). In the FM group, both anti-beta-LGB and ZO-1 were correlated significantly with physical and mental health components on the SF-36 scale (P < 0.05); whereas IL-1beta negatively correlated with the COMPASS-31 score (P < 0.05). In the ME/CFS cohort, ZO-1 was positively correlated with the COMPASS-31 score (P < 0.05). The ROC curve analysis indicated a strong ability of anti-β-LGB, ZO-1, LPS, and sCD14 to predictively distinguish between FM and ME/CFS from healthy controls (P < 0.0001).

Conclusions: Biomarkers of intestinal barrier function and inflammation were associated with autonomic dysfunction assessed by COMPASS-31 scores in FM and ME/CFS respectively. Anti-β-LGB antibodies, ZO-1, LPS, and sCD14 may be putative predictors of intestinal barrier dysfunction in these cohorts. Further studies are needed to assess whether these findings are causal and can therefore be applied in clinical practice.

Source: Franz Martin, Manuel Blanco Suárez2 Paola Zambrano, Óscar Cáceres Calle, Miriam Almirall, Jose Alegre-Martín, Beatriz Lobo, Ana María Gonzalez-Castro, Javier Santos, Joan Carles Domingo, Joanna Jurek, Jesús Castro-Marrero. Increased gut permeability and bacterial translocation are associated with fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome: implications for disease-related biomarker discovery. Front. Immunol., Sec. Mucosal Immunity, Volume 14 – 2023 | doi: 10.3389/fimmu.2023.1253121 https://www.frontiersin.org/articles/10.3389/fimmu.2023.1253121/abstract

A Clinical Qualification Protocol Highlights Overlapping Genomic Influences and Neuro-Autonomic Mechanisms in Ehlers-Danlos and Long COVID-19 Syndromes

Abstract:

A substantial fraction of the 15% with double-jointedness or hypermobility have the traditionally ascertained joint-skeletal, cutaneous, and cardiovascular symptoms of connective tissue dysplasia and its particular manifestation as Ehlers-Danlos syndrome (EDS). The holistic ascertainment of 120 findings in 1261 EDS patients added neuro-autonomic symptoms like headaches, muscle weakness, brain fog, chronic fatigue, dyspnea, and bowel irregularity to those of arthralgia and skin laxity, 15 of these symptoms shared with those of post-infectious SARS-CoV-2 (long COVID-19).

Underlying articulo-autonomic mechanisms guided a clinical qualification protocol that qualified DNA variants in 317 genes as having diagnostic utility for EDS, six of them identical (F2-LIFR-NLRP3-STAT1-T1CAM1-TNFRSF13B) and eighteen similar to those modifying COVID-19 severity/EDS, including ADAMTS13/ADAMTS2-C3/C1R-IKBKG/IKBKAP-PIK3C3/PIK3R1-POLD4/POLG-TMPRSS2/TMPRSS6-WNT3/WNT10A.

Also, contributing to EDS and COVID-19 severity were forty and three genes, respectively, impacting mitochondrial functions as well as parts of an overlapping gene network, or entome, that are hypothesized to mediate the cognitive-behavioral, neuro-autonomic, and immune-inflammatory alterations of connective tissue in these conditions. The further characterization of long COVID-19 natural history and genetic predisposition will be necessary before these parallels to EDS can be carefully delineated and translated into therapies.

Source: Wilson GN. A Clinical Qualification Protocol Highlights Overlapping Genomic Influences and Neuro-Autonomic Mechanisms in Ehlers-Danlos and Long COVID-19 Syndromes. Curr Issues Mol Biol. 2023 Jul 17;45(7):6003-6023. doi: 10.3390/cimb45070379. PMID: 37504295; PMCID: PMC10378515. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10378515/ (Full text)

Vagus nerve inflammation contributes to dysautonomia in COVID-19

Abstract:

Dysautonomia has substantially impacted acute COVID-19 severity as well as symptom burden after recovery from COVID-19 (long COVID), yet the underlying causes remain unknown. Here, we hypothesized that vagus nerves are affected in COVID-19 which might contribute to autonomic dysfunction.

We performed a histopathological characterization of postmortem vagus nerves from COVID-19 patients and controls, and detected SARS-CoV-2 RNA together with inflammatory cell infiltration composed primarily of monocytes. Furthermore, we performed RNA sequencing which revealed a strong inflammatory response of neurons, endothelial cells, and Schwann cells which correlated with SARS-CoV-2 RNA load. Lastly, we screened a clinical cohort of 323 patients to detect a clinical phenotype of vagus nerve affection and found a decreased respiratory rate in non-survivors of critical COVID-19.

Our data suggest that SARS-CoV-2 induces vagus nerve inflammation followed by autonomic dysfunction which contributes to critical disease courses and might contribute to dysautonomia observed in long COVID.

Source:Woo MS, Shafiq M, Fitzek A, Dottermusch M, Altmeppen H, Mohammadi B, Mayer C, Bal LC, Raich L, Matschke J, Krasemann S, Pfefferle S, Brehm TT, Lütgehetmann M, Schädler J, Addo MM, Schulze Zur Wiesch J, Ondruschka B, Friese MA, Glatzel M. Vagus nerve inflammation contributes to dysautonomia in COVID-19. Acta Neuropathol. 2023 Jul 15. doi: 10.1007/s00401-023-02612-x. Epub ahead of print. PMID: 37452829. https://link.springer.com/article/10.1007/s00401-023-02612-x (Full text)

Persistent post-COVID-19 neuromuscular symptoms

Abstract:

Neuromuscular symptoms may develop or persist after resolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Besides residual sensorimotor symptoms associated with acute neuromuscular complications of coronavirus disease-2019 (COVID-19), such as Guillain-Barré syndrome, critical illness neuromyopathy, and rhabdomyolysis, patients may report persistent autonomic symptoms, sensory symptoms, and muscle symptoms in the absence of these acute complications, including palpitations, orthostatic dizziness and intolerance, paresthesia, myalgia, and fatigue.

These symptoms may be associated with long COVID, also known as post-COVID-19 conditions or postacute sequelae of SARS-CoV-2 infection, which may significantly impact quality of life. Managing these symptoms represents a challenge for health-care providers.

Recent advances have identified small-fiber neuropathy as a potential etiology that may underlie autonomic dysfunction and paresthesia in some long COVID patients. The pathogenic mechanisms underlying myalgia and fatigue remain elusive and need to be investigated. Herein we review the current state of knowledge regarding the evaluation and management of patients with persistent post-COVID-19 neuromuscular symptoms.

Source: Abrams RMC, Zhou L, Shin SC. Persistent post-COVID-19 neuromuscular symptoms. Muscle Nerve. 2023 Jul 19. doi: 10.1002/mus.27940. Epub ahead of print. PMID: 37466117. https://onlinelibrary.wiley.com/doi/10.1002/mus.27940 (Full text)

Evaluation of Outpatients in the Post-COVID-19 Period in Terms of Autonomic Dysfunction and Silent Ischemia

Abstract:

Introduction and objective: In this context, the objective of this study is to evaluate the 24-hour ambulatory electrocardiography (ECG) recordings, autonomous function with heart rate variability (HRV), and silent ischemia (SI) attacks with ST depression burden (SDB) and ST depression time (SDT) of post-COVID-19 patients. Materials and methods: The 24-hour ambulatory ECG recordings obtained >12 weeks after the diagnosis of COVID-19 were compared between 55 consecutive asymptomatic and 73 symptomatic post-COVID-19 patients who applied to the cardiology outpatient clinic with complaints of palpitation and chest pain in comparison with asymptomatic post-COVID-19 patients in Kars Harakani state hospital. SDB, SDT, and HRV parameters were analyzed. Patients who had been on medication that might affect HRV, had comorbidities that might have caused coronary ischemia, and were hospitalized with severe COVID-19 were excluded from the study.

Results: There was no significant difference between symptomatic and asymptomatic post-COVID-19 patients in autonomic function. On the other hand, SDB and SDT parameters were significantly higher in symptomatic post-COVID-19 patients than in asymptomatic post-COVID-19 patients. Multivariate analysis indicated that creatine kinase-myoglobin binding (CK-MB) (OR:1.382, 95% CI:1.043-1.831; p=0.024) and HRV index (OR: 1.033, 95% CI:1.005-1.061; p=0.019) were found as independent predictors of palpitation and chest pain symptoms in post-COVID-19 patients.

Conclusion: The findings of this study revealed that parasympathetic overtone and increased HRV were significantly higher in symptomatic patients with a history of COVID-19 compared to asymptomatic patients with a history of COVID-19 in the post-COVID-19 period. Additionally, 24-hour ambulatory ECG recordings and ST depression analysis data indicated that patients who experienced chest pain in the post-COVID-19 period experienced silent ischemia (SI) attacks.

Source: Karakayalı M, Artac I, Ilis D, Omar T, Rencuzogullari I, Karabag Y, Altunova M, Arslan A, Guzel E. Evaluation of Outpatients in the Post-COVID-19 Period in Terms of Autonomic Dysfunction and Silent Ischemia. Cureus. 2023 Jun 11;15(6):e40256. doi: 10.7759/cureus.40256. PMID: 37440812; PMCID: PMC10335598. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10335598/ (Full text)

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)

Vagus Nerve Dysfunction in the Post-COVID-19 Condition

Abstract:

Background: The post-COVID-19 condition (PCC) is a disabling syndrome affecting 5-15% of subjects who survive COVID-19. SARS-CoV-2 mediated vagus nerve dysfunction could explain some of the PCC symptoms, including persistent dysphonia, dysphagia, dyspnea, dizziness, tachycardia, orthostatic hypotension, gastrointestinal disturbances or neurocognitive complaints.

Methods: We performed a cross-sectional pilot study in subjects with PCC with symptoms suggesting vagus nerve dysfunction (n=30) and compared them to subjects fully recovered from acute COVID-19 (n=14) and individuals never infected with SARS-CoV-2 (n=16), matched by age and sex. We evaluated the structure and function of the vagus nerve, including dysphonia, dysphagia, and dysautonomia tests, and evaluated the structure and function of respiratory muscles with vagus nerve innervation.

Findings: Participants were mostly (80%) women with median 44 years of age. Their most prevalent symptoms were cognitive dysfunction (83%), dyspnea (80%) and tachycardia (80%). Compared with COVID-19-recovered and uninfected controls, respectively, subjects with PCC were more likely to show thickening and hyperechogenic vagus nerve in neck ultrasounds (mean ± SD left vagus nerve cross-sectional area: 2.4 ± 0.97mm2 vs. 2 ± 0.52mm2 vs. 1.9 ± 0.73 mm2, p=0.080), flattened diaphragmatic curve (47% vs 6% vs 14%, p=0.007), reduced esophageal peristalsis (34% vs 0% vs 21%, p=0.020), gastroesophageal reflux (34% vs 19% vs 7%, p=0.130), hiatal hernia (25% vs 0% vs 7%, p=0.050) and reduced maximal inspiratory pressure in functional respiratory tests (62% vs. 6% vs. 17%, p ≤0.001).

Interpretation: Vagus nerve dysfunction has a central pathogenic role in the pathophysiology of the post-COVID condition.

Source: Lladós, Gemma and Massanella, Marta and Coll-Fernández, Roser and Rodríguez, Raúl and Hernández, Electra and Lucente, Giuseppe and López, Cristina and Loste, Cora and Santos, José Ramón and España-Cueto, Sergio and Nevot, Maria and Muñoz-López, Francisco and Arrieta, Sandra Silva and Brander, Christian and Durà, Maria José and Cuadras, Patricia and Bechini, Jordi and Tenesa, Montserrat and Martinez-Piñeiro, Alicia and Herrero, Cristina and Chamorro, Anna and Garcia, Anna and Grau, Eulalia and Clotet, Bonaventura and Paredes, Roger and Mateu, Lourdes and Unit, Germans Trias Long-COVID, Vagus Nerve Dysfunction in the Post-COVID-19 Condition. Available at SSRN: https://ssrn.com/abstract=4479598 or http://dx.doi.org/10.2139/ssrn.4479598

Clinical Features of Post-Covid Syndrome

Abstract:

There is no common understanding of the clinical picture of post-covid syndrome. The US regulator CDC proposes to highlight:

(A) persistent symptoms and conditions that begin during acute COVID-19 illness;

B) new onset late complications after asymptomatic disease or a period of acute symptomatic relief or remission;

(C) the evolution of symptoms and conditions that include some persistent symptoms (eg, shortness of breath) with the addition of new symptoms or conditions over time (eg, cognitive difficulties).

Some manifestations may resemble other postviral syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome, dysautonomia (eg, postural orthostatic tachycardia syndrome), or mast cell activation syndrome.

Source: Sayfulloyevich, P. S. ., & Musayevich, U. R. . (2023). Clinical Features of Post-Covid Syndrome. EUROPEAN JOURNAL OF INNOVATION IN NONFORMAL EDUCATION, 3(6), 34–36. Retrieved from http://inovatus.es/index.php/ejine/article/view/1786 http://inovatus.es/index.php/ejine/article/view/1786/1794 (Full text)