nach oben

Erschienen in:

28.09.2022 | COVID-19 | Original Article

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

verfasst von: Peter Novak, Matthew P. Giannetti, Emily Weller, Matthew J. Hamilton, Shibani S. Mukerji, Haitham S. Alabsi, David Systrom, Sadie P. Marciano, Donna Felsenstein, William J. Mullally, David M. Pilgrim, Mariana Castells

Erschienen in: Neurological Sciences | Ausgabe 12/2022

Einloggen, um Zugang zu erhalten

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.

Nur mit Berechtigung zugänglich

Ewing DJ, Clarke BF (1982) Diagnosis and management of diabetic autonomic neuropathy. Br Med J Clin Res Ed 285:916–918. https://doi.org/10.1136/bmj.285.6346.916CrossRefPubMedPubMedCentral

Novak P (2011) Quantitative autonomic testing. J Vis Exp JoVE. https://doi.org/10.3791/2502CrossRefPubMed

Low PA, Tomalia VA, Park K-J (2013) Autonomic function tests: some clinical applications. J Clin Neurol Seoul Korea 9:1–8. https://doi.org/10.3988/jcn.2013.9.1.1CrossRef

Novak P (2019) Autonomic Testing, Oxford University Press

Calder PC, Bosco N, Bourdet-Sicard R, Capuron L, Delzenne N, Doré J, Franceschi C, Lehtinen MJ, Recker T, Salvioli S, Visioli F (2017) Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition. Ageing Res Rev 40:95–119. https://doi.org/10.1016/j.arr.2017.09.001CrossRefPubMed

Masoli JAH, Delgado J (2021) Blood pressure, frailty and dementia. Exp Gerontol 155:111557. https://doi.org/10.1016/j.exger.2021.111557CrossRefPubMed

Lopez Angel CJ, Pham EA, Du H, Vallania F, Fram BJ, Perez K, Nguyen T, Rosenberg-Hasson Y, Ahmed A, Dekker CL, Grant PM, Khatri P, Maecker HT, Glenn JS, Davis MM, Furman D (2021) Signatures of immune dysfunction in HIV and HCV infection share features with chronic inflammation in aging and persist after viral reduction or elimination. Proc Natl Acad Sci U S A 118:e2022928118. https://doi.org/10.1073/pnas.2022928118CrossRefPubMedPubMedCentral

Coutinho BM, Bordalo E, Nascimento OJM (2013) Autonomic evaluation of hepatitis C virus infected patients. Arq Neuropsiquiatr 71:537–539. https://doi.org/10.1590/0004-282X20130074CrossRefPubMed

Siepmann T, Penzlin AI, Illigens BMW (2013) Autonomic neuropathies. Dtsch Med Wochenschr 1946(138):1465–1469. https://doi.org/10.1055/s-0033-1343268CrossRef

10.

Ristikj-Stomnaroska D, Risteska-Nejashmikj V, Papazova M (2019) Role of inflammation in the pathogenesis of diabetic peripheral neuropathy, Open Access Maced. J Med Sci 7:2267–2270. https://doi.org/10.3889/oamjms.2019.646CrossRef

11.

Chowdhury M, Nevitt S, Eleftheriadou A, Kanagala P, Esa H, Cuthbertson DJ, Tahrani A, Alam U (2021) Cardiac autonomic neuropathy and risk of cardiovascular disease and mortality in type 1 and type 2 diabetes: a meta-analysis. BMJ Open Diabetes Res Care 9:e002480. https://doi.org/10.1136/bmjdrc-2021-002480CrossRefPubMedPubMedCentral

12.

Schofield JR, Chemali KR (2019) Intravenous immunoglobulin therapy in refractory autoimmune dysautonomias: a retrospective analysis of 38 patients. Am J Ther 26:570–582. https://doi.org/10.1097/MJT.0000000000000778CrossRefPubMed

13.

Rodriguez B, Hoepner R, Salmen A, Kamber N, Z’Graggen WJ (2021) Immunomodulatory treatment in postural tachycardia syndrome: A case series. Eur J Neurol 28:1692–1697. https://doi.org/10.1111/ene.14711CrossRefPubMed

14.

Trevino JA, Novak P (2021) TS-HDS and FGFR3 antibodies in small fiber neuropathy and Dysautonomia. Muscle Nerve 64:70–76. https://doi.org/10.1002/mus.27245CrossRefPubMed

15.

Levine TD, Kafaie J, Zeidman LA, Saperstein DS, Massaquoi R, Bland RJ, Pestronk A (2019) Cryptogenic small-fiber neuropathies: serum autoantibody binding to trisulfated heparan disaccharide and fibroblast growth factor receptor-3. Muscle Nerve. https://doi.org/10.1002/mus.26748CrossRefPubMed

16.

Liu X, Treister R, Lang M, Oaklander AL (2018) IVIg for apparently autoimmune small-fiber polyneuropathy: first analysis of efficacy and safety. Ther Adv Neurol Disord 11. https://doi.org/10.1177/1756285617744484

17.

Geerts M, de Greef BTA, Sopacua M, van Kuijk SMJ, Hoeijmakers JGJ, Faber CG, Merkies ISJ (2021) intravenous immunoglobulin therapy in patients with painful idiopathic small fiber Neuropathy. Neurology 96:e2534–e2545. https://doi.org/10.1212/WNL.0000000000011919CrossRefPubMedPubMedCentral

18.

Kim J, Yoon S, Lee S, Hong H, Ha E, Joo Y, Lee EH, Lyoo IK (2020) A double-hit of stress and low-grade inflammation on functional brain network mediates posttraumatic stress symptoms. Nat Commun 11:1898. https://doi.org/10.1038/s41467-020-15655-5CrossRefPubMedPubMedCentral

19.

Birt HWG, Dennis PG (2021) Inference and analysis of SPIEC-EASI microbiome networks, methods Mol. Biol Clifton NJ 2232:155–171. https://doi.org/10.1007/978-1-0716-1040-4_14CrossRef

20.

Jeong H, Mason SP, Barabási AL, Oltvai ZN (2001) Lethality and centrality in protein networks. Nature 411:41–42. https://doi.org/10.1038/35075138CrossRefPubMed

21.

Hevey D (n.d.) Network analysis: A brief overview and tutorial. Health Psychol Behav Med 6 301–328. https://doi.org/10.1080/21642850.2018.1521283

22.

Bisaccia G, Ricci F, Recce V, Serio A, Iannetti G, Chahal AA, Ståhlberg M, Khanji MY, Fedorowski A, Gallina S (2021) Post-acute sequelae of COVID-19 and cardiovascular autonomic dysfunction: what do we know? J Cardiovasc Dev Dis 8:156. https://doi.org/10.3390/jcdd8110156CrossRefPubMedPubMedCentral

23.

Novak P, Mukerji SS, Alabsi HS, Systrom D, Marciano SP, Felsenstein D, Mullally WJ, Pilgrim DM (2022) Multisystem involvement in post-acute sequelae of coronavirus disease 19. Ann Neurol 91:367–379. https://doi.org/10.1002/ana.26286CrossRefPubMedPubMedCentral

24.

Garland EM, Celedonio JE, Raj SR (2015) Postural tachycardia syndrome: beyond orthostatic intolerance. Curr Neurol Neurosci Rep 15:60. https://doi.org/10.1007/s11910-015-0583-8CrossRefPubMedPubMedCentral

25.

Bornstein SR, Voit-Bak K, Donate T, Rodionov RN, Gainetdinov RR, Tselmin S, Kanczkowski W, Müller GM, Achleitner M, Wang J, Licinio J, Bauer M, Young AH, Thuret S, Bechmann N, Straube R (2021) Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis? Mol Psychiatry 1–4. https://doi.org/10.1038/s41380-021-01148-4

26.

Mistry D, Wise RP, Dickerson JA (2017) DiffSLC: A graph centrality method to detect essential proteins of a protein-protein interaction network. PLoS One 12:e0187091. https://doi.org/10.1371/journal.pone.0187091CrossRefPubMedPubMedCentral

27.

Kojaku S, Masuda N (2019) Constructing networks by filtering correlation matrices: a null model approach. Proc Math Phys Eng Sci 475:20190578. https://doi.org/10.1098/rspa.2019.0578CrossRefPubMedPubMedCentral

28.

Borgatti S (2005) Centrality and network flow. Soc Netw 27:55–71. https://doi.org/10.1016/j.socnet.2004.11.008CrossRef

29.

Freeman L (1977) A set of measures of centrality based on betweeneness. Sociometry 40:35–41. https://doi.org/10.2307/3033543CrossRef

30.

Bavelas A (1950) Communication patterns in task-oriented groups. J Acoust Soc Am 22:725–730. https://doi.org/10.1121/1.1906679CrossRef

31.

Sabidussi G (1966) The centrality of a graph. Psychometrika 31:581–603. https://doi.org/10.1007/BF02289527CrossRefPubMed

32.

Nieminen J (1974) On the centrality in a graph. Scand J Psychol 15:332–336. https://doi.org/10.1111/j.1467-9450.1974.tb00598.xCrossRefPubMed

33.

Austin PC, White IR, Lee DS, van Buuren S (2020) Missing data in clinical research: a tutorial on multiple imputation. Can J Cardiol S0828–282X(20)31111–9. https://doi.org/10.1016/j.cjca.2020.11.010

34.

Novak P (2011) Assessment of sympathetic index from the Valsalva maneuver. Neurology 76:2010–2016. https://doi.org/10.1212/WNL.0b013e31821e5563CrossRefPubMedPubMedCentral

35.

Novak P (2022) Qpack-a Python package for QASAT-quantitative scale for grading cerebral blood flow, autonomic testing, and skin biopsies. Neurol Sci Off J Ital Neurol Soc Ital Soc Clin Neurophysiol. https://doi.org/10.1007/s10072-022-06007-wCrossRef

36.

Bastyr EJ, Price KL, Bril V (2005) MBBQ Study Group, development and validity testing of the neuropathy total symptom score-6: questionnaire for the study of sensory symptoms of diabetic peripheral neuropathy. Clin Ther 27:1278–1294. https://doi.org/10.1016/j.clinthera.2005.08.002CrossRefPubMed

37.

Zilliox L, Peltier AC, Wren PA, Anderson A, Smith AG, Singleton JR, Feldman EL, Alexander NB, Russell JW (2011) Assessing autonomic dysfunction in early diabetic neuropathy: the Survey of Autonomic Symptoms. Neurology 76:1099–1105. https://doi.org/10.1212/WNL.0b013e3182120147CrossRefPubMedPubMedCentral

38.

Novak P, Mukerji SS, Alabsi HS, Systrom D, Marciano SP, Felsenstein D, Mullally WJ, Pilgrim DM (2021) Multisystem involvement in post-acute sequelae of COVID-19 (PASC). Ann Neurol. https://doi.org/10.1002/ana.26286CrossRef

39.

Novak P (2017) Electrochemical skin conductance: a systematic review. Clin Auton Res Off J Clin Auton Res Soc. https://doi.org/10.1007/s10286-017-0467-xCrossRef

40.

Lauria G, Hsieh ST, Johansson O, Kennedy WR, Leger JM, Mellgren SI, Nolano M, Merkies ISJ, Polydefkis M, Smith AG, Sommer C, Valls-Solé J (2010) European Federation of Neurological Societies, Peripheral Nerve Society, European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol 17:903–912, e44–49. https://doi.org/10.1111/j.1468-1331.2010.03023.x

41.

Novak P, Mukerji S, Alabsi H, Systrom D (2022) Multisystem involvement in post-acute sequelae of COVID-19 (PASC). Ann Neurol

42.

Hu B, Yang X-R, Xu Y, Sun Y-F, Sun C, Guo W, Zhang X, Wang W-M, Qiu S-J, Zhou J, Fan J (2014) Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res Off J Am Assoc Cancer Res 20:6212–6222. https://doi.org/10.1158/1078-0432.CCR-14-0442CrossRef

43.

Bonaccio M, Di Castelnuovo A, Pounis G, De Curtis A, Costanzo S, Persichillo M, Cerletti C, Donati MB, de Gaetano G, Iacoviello L (2016) Moli-sani Study Investigators, A score of low-grade inflammation and risk of mortality: prospective findings from the Moli-sani study. Haematologica 101:1434–1441. https://doi.org/10.3324/haematol.2016.144055CrossRefPubMedPubMedCentral

44.

Kauffman J, Kittas A, Bennett L, Tsoka S (2014) DyCoNet: a Gephi plugin for community detection in dynamic complex networks. PLoS One 9:e101357. https://doi.org/10.1371/journal.pone.0101357CrossRefPubMedPubMedCentral

45.

Pollard TJ, Johnson AEW, Raffa JD, Mark RG (2018) tableone: an open source Python package for producing summary statistics for research papers. JAMIA Open 1:26–31. https://doi.org/10.1093/jamiaopen/ooy012CrossRefPubMedPubMedCentral

46.

Novak P, Giannetti M, Weller E, Hamilton M, Castells M (2021) Mast cell disorders are associated with decreased cerebral blood flow and small fiber neuropathy. Ann Allergy Asthma Immunol Off Publ Am Coll Allergy Asthma Immunol S1081–1206(21):01155–8. https://doi.org/10.1016/j.anai.2021.10.006CrossRef

47.

van Campen CLMC, Rowe PC, Visser FC (2021) Orthostatic symptoms and reductions in cerebral blood flow in long-haul COVID-19 patients: similarities with myalgic encephalomyelitis/chronic fatigue syndrome. Med Kaunas Lith 58:28. https://doi.org/10.3390/medicina58010028CrossRef

48.

Wood J, Tabacof L, Tosto-Mancuso J, McCarthy D, Kontorovich A, Putrino D (2021) Levels of end-tidal carbon dioxide are low despite normal respiratory rate in individuals with long COVID. J Breath Res 16. https://doi.org/10.1088/1752-7163/ac3c18

49.

Abrams RMC, Simpson DM, Navis A, Jette N, Zhou L, Shin SC (2021) Small fiber neuropathy associated with SARS-CoV-2 infection. Muscle Nerve. https://doi.org/10.1002/mus.27458CrossRefPubMedPubMedCentral

50.

Oaklander AL, Mills AJ, Kelley M, Toran LS, Smith B, Dalakas MC, Nath A (2022) Peripheral neuropathy evaluations of patients with prolonged long COVID. Neurol Neuroimmunol Neuroinflammation 9:e1146. https://doi.org/10.1212/NXI.0000000000001146CrossRef

51.

Shouman K, Vanichkachorn G, Cheshire WP, Suarez MD, Shelly S, Lamotte GJ, Sandroni P, Benarroch EE, Berini SE, Cutsforth-Gregory JK, Coon EA, Mauermann ML, Low PA, Singer W (2021) Autonomic dysfunction following COVID-19 infection: an early experience. Clin Auton Res Off J Clin Auton Res Soc 31:385–394. https://doi.org/10.1007/s10286-021-00803-8CrossRef

52.

Reardon C, Murray K, Lomax AE (2018) Neuroimmune communication in health and disease. Physiol Rev 98:2287–2316. https://doi.org/10.1152/physrev.00035.2017CrossRefPubMedPubMedCentral

53.

O’Mahony C, van der Kleij H, Bienenstock J, Shanahan F, O’Mahony L (2009) Loss of vagal anti-inflammatory effect: in vivo visualization and adoptive transfer. Am J Physiol Regul Integr Comp Physiol 297:R1118-1126. https://doi.org/10.1152/ajpregu.90904.2008CrossRefPubMed

54.

Grimes T, Potter SS, Datta S (2019) Integrating gene regulatory pathways into differential network analysis of gene expression data. Sci Rep 9:5479. https://doi.org/10.1038/s41598-019-41918-3CrossRefPubMedPubMedCentral

55.

Sollini M, Morbelli S, Ciccarelli M, Cecconi M, Aghemo A, Morelli P, Chiola S, Gelardi F, Chiti A (2021) Long COVID hallmarks on [18F]FDG-PET/CT: a case-control study. Eur J Nucl Med Mol Imaging 1–11. https://doi.org/10.1007/s00259-021-05294-3

56.

Christensen RH, Berg RMG (2021)Vascular inflammation as a therapeutic target in COVID-19 “Long Haulers”: HIITing the Spot? Front Cardiovasc Med 8. https://www.frontiersin.org/article/10.3389/fcvm.2021.643626. Accessed 23 Jun 2022

Titel: Network autonomic analysis of post-acute sequelae of COVID-19 and postural tachycardia syndrome
verfasst von: Peter Novak
Matthew P. Giannetti
Emily Weller
Matthew J. Hamilton
Shibani S. Mukerji
Haitham S. Alabsi
David Systrom
Sadie P. Marciano
Donna Felsenstein
William J. Mullally
David M. Pilgrim
Mariana Castells
Publikationsdatum: 28.09.2022
Verlag: Springer International Publishing
Schlagwort: COVID-19
Erschienen in: Neurological Sciences / Ausgabe 12/2022
Print ISSN: 1590-1874
Elektronische ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-022-06423-y

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Schützt Olivenöl vor dem Tod durch Demenz?

10.05.2024 Morbus Alzheimer Nachrichten

Konsumieren Menschen täglich 7 Gramm Olivenöl, ist ihr Risiko, an einer Demenz zu sterben, um mehr als ein Vierten reduziert – und dies weitgehend unabhängig von ihrer sonstigen Ernährung. Dafür sprechen Auswertungen zweier großer US-Studien.

Bluttest erkennt Parkinson schon zehn Jahre vor der Diagnose

10.05.2024 Parkinson-Krankheit Nachrichten

Ein Bluttest kann abnorm aggregiertes Alpha-Synuclein bei einigen Menschen schon zehn Jahre vor Beginn der motorischen Parkinsonsymptome nachweisen. Mit einem solchen Test lassen sich möglicherweise Prodromalstadien erfassen und die Betroffenen früher behandeln.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Wartezeit nicht kürzer, aber Arbeit flexibler

Psychotherapie Medizin aktuell

Fünf Jahren nach der Neugestaltung der Psychotherapie-Richtlinie wurden jetzt die Effekte der vorgenommenen Änderungen ausgewertet. Das Hauptziel der Novellierung war eine kürzere Wartezeit auf Therapieplätze. Dieses Ziel wurde nicht erreicht, es gab jedoch positive Auswirkungen auf andere Bereiche.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Abstract

Background

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2022

Inflammatory markers and depression in Parkinson’s disease: a systematic review

Real-time data on the prognosis of acute ischemic stroke patients in the Tochigi Clinical ObservatioNal registry for 1-year mortality of aCute ischEmic stRoke patieNt (T-CONCERN) study

Favorable outcome of partial splenic embolization after thrombolysis-induced splenic rupture following ischemic stroke: a case report

Repetitive transcranial magnetic stimulation (rTMS) for post-stroke sleep disorders: a systematic review of randomized controlled trials

Progressive motor neuron syndromes with single CNS lesions and CSF oligoclonal bands: never forget solitary sclerosis!