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Sympathetic cardiovascular and sudomotor functions are frequently affected in early multiple sclerosis

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Abstract

Objective

The aim of this study was to determine the prevalence of autonomic dysfunction using the composite autonomic scoring scale (CASS) and heart rate variability (HRV) in patients with clinically isolated syndrome (CIS) and to correlate autonomic dysfunction with other measures of MS disease activity.

Methods

CASS, HRV and plasma catecholamines during supine and tilted phase were performed in 104 CIS patients. MRI findings were analyzed for total number of lesions and the presence of brainstem and cervical spinal cord lesions.

Results

Autonomic dysfunction (CASS >1) was present in 59.8 % of patients, parasympathetic dysfunction in 5 %, sympathetic in 42.6 % and sudomotor in 32.7 % of patients. Patients with autonomic dysfunction on CASS had lower level of norepinephrine in the supine position compared to patients without autonomic dysfunction (1.06 ± 0.53 vs. 1.37 ± 0.86, p = 0.048). The CASS score showed positive correlation with s-HF (r = 0.226, p = 0.031), s-SDNN (r = 0.221, p = 0.035), t-HF (r = 0.225, p = 0.032), and t-HFnu (r = 0.216, p = 0.04), and a negative correlation with t-LF/HF (r = −0.218, p = 0.038). More patients with MRI brainstem lesions had a positive adrenergic index (p = 0.038). Patients with MRI brainstem lesions also had a lower t-SDNN (26.2 ± 14.2 vs. 32 ± 13.3, p = 0.036) and a lower t-LF (median 415.0 vs. 575.5, p = 0.018) compared to patients without these lesions. Patients with adrenergic index ≥1 had a significantly higher standing heart rate compared to patients with an adrenergic index of 0 (96 ± 13.5 vs. 90 ± 12, p = 0.032).

Conclusion

Autonomic (primarily sympathetic) dysfunction is present in a large proportion of early MS patients and it seems to be related to brainstem involvement.

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Abbreviations

ANS:

Autonomic nervous system

CIS:

Clinically isolated syndrome

MS:

Multiple sclerosis

MRI:

Magnetic resonance imaging

CASS:

Composite autonomic scoring scale

HRV:

Heart rate variability

QSART:

Quantitative sudomotor axon reflex test

TFM:

Task force monitor

HF:

High frequency

LF:

Low frequency

nu:

Normalized units

HR:

Heart rate

sBP:

Systolic blood pressure

dBP:

Diastolic blood pressure

BS:

Brainstem

References

  1. Brownlee WJ, Miller DH (2014) Clinically isolated syndromes and the relationship to multiple sclerosis. J Clin Neurosci 21:2065–2071

    Article  PubMed  Google Scholar 

  2. Adamec I, Habek M (2013) Autonomic dysfunction in multiple sclerosis. Clin Neurol Neurosurg 115(Suppl 1):S73–S78

    Article  PubMed  Google Scholar 

  3. Racosta JM, Sposato LA, Morrow SA, Cipriano L, Kimpinski K, Kremenchutzky M (2015) Cardiovascular autonomic dysfunction in multiple sclerosis: a meta-analysis. Mult Scler Relat Disord 4:104–111

    Article  PubMed  Google Scholar 

  4. Low PA (1993) Composite autonomic scoring scale for laboratory quantification of generalized autonomic failure. Mayo Clin Proc 68:748–752

    Article  CAS  PubMed  Google Scholar 

  5. Crnošija L, Adamec I, Lovrić M et al (2016) Autonomic dysfunction in clinically isolated syndrome suggestive of multiple sclerosis. Clin Neurophysiol 127:864–869

    Article  PubMed  Google Scholar 

  6. Flachenecker P, Reiners K, Krauser M, Wolf A, Toyka KV (2001) Autonomic dysfunction in multiple sclerosis is related to disease activity and progression of disability. Mult Scler 7:327–334

    Article  CAS  PubMed  Google Scholar 

  7. Novak P (2011) Quantitative autonomic testing. J Vis Exp (53).doi:10.3791/2502

  8. Freeman R (2006) Assessment of cardiovascular autonomic function. Clin Neurophysiol 117:716–730

    Article  PubMed  Google Scholar 

  9. Tarvainen MP, Niskanen JP, Lipponen JA, Ranta-Aho PO, Karjalainen PA (2014) Kubios HRV–heart rate variability analysis software. Comput Methods Programs Biomed 113:210–220

    Article  PubMed  Google Scholar 

  10. Malik M, Bigger JT, Camm AJ et al (1996) Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 17:354–381

  11. Sztajzel J (2004) Heart rate variability: a noninvasive electrocardiographic method to measure the autonomic nervous system. Swiss Med Wkly 134:514–522

    PubMed  Google Scholar 

  12. Nasseri K, Uitdehaag BM, van Walderveen MA, Ader HJ, Polman CH (1999) Cardiovascular autonomic function in patients with relapsing remitting multiple sclerosis: a new surrogate marker of disease evolution? Eur J Neurol 6:29–33

    Article  CAS  PubMed  Google Scholar 

  13. Saari A, Tolonen U, Pääkkö E, Suominen K, Pyhtinen J, Sotaniemi K, Myllylä V (2004) Cardiovascular autonomic dysfunction correlates with brain MRI lesion load in MS. Clin Neurophysiol 115:1473–1478

    Article  CAS  PubMed  Google Scholar 

  14. Zoukos Y, Thomaides T, Pavitt DV, Leonard JP, Cuzner ML, Mathias CJ (1992) Up-regulation of beta-adrenoceptors on circulating mononuclear cells after reduction of central sympathetic outflow by clonidine in normal subjects. Clin Auton Res 2:165–170

    Article  CAS  PubMed  Google Scholar 

  15. Polak PE, Kalinin S, Feinstein DL (2011) Locus coeruleus damage and noradrenaline reductions in multiple sclerosis and experimental autoimmune encephalomyelitis. Brain 134:665–677

    Article  PubMed  PubMed Central  Google Scholar 

  16. Rajda C, Bencsik K, Fuvesi J, Seres E, Vecsei L, Bergquist J (2006) The norepinephrine level is decreased in the lymphocytes of long-term interferon-beta-treated multiple sclerosis patients. Mult Scler 12:265–270

    Article  CAS  PubMed  Google Scholar 

  17. Sternberg Z (2016) Impaired neurovisceral integration of cardiovascular modulation contributes to multiple sclerosis morbidities. Mol Neurobiol. doi:10.1007/s12035-015-9599-y

    PubMed  Google Scholar 

  18. Davis SL, Wilson TE, Vener JM, Crandall CG, Petajan JH, White AT (1985) Pilocarpine-induced sweat gland function in individuals with multiple sclerosis. J Appl Physiol 2005(98):1740–1744

    Google Scholar 

  19. Gotoh F, Komatsumoto S, Araki N, Gomi S (1984) Noradrenergic nervous activity in migraine. Arch Neurol 41:951–955

    Article  CAS  PubMed  Google Scholar 

  20. Gomi S, Gotoh F, Komatsumoto S, Ishikawa Y, Araki N, Hamada J (1989) Sweating function and retinal vasomotor reactivity in migraine. Cephalalgia 9:179–185

    Article  CAS  PubMed  Google Scholar 

  21. Vasheghani-Farahani A, Sahraian MA, Darabi L, Aghsaie A, Minagar A (2011) Incidence of various cardiac arrhythmias and conduction disturbances due to high dose intravenous methylprednisolone in patients with multiple sclerosis. J Neurol Sci 309:75–78

    Article  CAS  PubMed  Google Scholar 

  22. Rossi S, Rocchi C, Studer V, Motta C et al (2015) The autonomic balance predicts cardiac responses after the first dose of fingolimod. Mult Scler 21:206–216

    Article  CAS  PubMed  Google Scholar 

  23. Hilz MJ, Intravooth T, Moeller S, Wang R, Lee DH, Koehn J, Linker RA (2015) Central autonomic dysfunction delays recovery of fingolimod induced heart rate slowing. PLoS One 10:e0132139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Huang M, Jay O, Davis SL (2015) Autonomic dysfunction in multiple sclerosis: implications for exercise. Auton Neurosci 188:82–85

    Article  PubMed  Google Scholar 

  25. Thomaides TN, Zoukos Y, Chaudhuri KR, Mathias CJ (1993) Physiological assessment of aspects of autonomic function in patients with secondary progressive multiple sclerosis. J Neurol 240:139–143

    Article  CAS  PubMed  Google Scholar 

  26. Pepin EB, Hicks RW, Spencer MK, Tran ZV, Jackson CG (1996) Pressor response to isometric exercise in patients with multiple sclerosis. Med Sci Sports Exerc 28:656–660

    Article  CAS  PubMed  Google Scholar 

  27. Senaratne MP, Carroll D, Warren KG, Kappagoda T (1984) Evidence for cardiovascular autonomic nerve dysfunction in multiple sclerosis. J Neurol Neurosurg Psychiatry 47:947–952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cohen JA, Hossack KF, Franklin GM (1989) Multiple sclerosis patients with fatigue: relationship among temperature regulation, autonomic dysfunction, and exercise capacity. Neurorehabil Neural Repair 3:193–198

    Article  Google Scholar 

  29. Huang M, Morris NB, Jay O, Davis SL. Thermoregulatory dysfunction in multiple sclerosis patients during moderate exercise in a thermoneutral environment. FASEB J 2014;28 (Supplement 1),1104.17

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Authors and Affiliations

  1. School of Medicine, University of Zagreb, Zagreb, Croatia

    Mario Habek & Luka Crnošija

  2. Department of Neurology, Referral Center for Autonomic Nervous System Disorders, University Hospital Center Zagreb, Zagreb, Croatia

    Mario Habek, Anamari Junaković, Magdalena Krbot Skorić & Ivan Adamec

  3. Department of Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia

    Mila Lovrić

  4. University Department of Neurology, University Hospital Center Zagreb, Kišpatićeva 12, 10000, Zagreb, Croatia

    Mario Habek

Authors
  1. Mario Habek
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  2. Luka Crnošija
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  3. Mila Lovrić
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  4. Anamari Junaković
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  5. Magdalena Krbot Skorić
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  6. Ivan Adamec
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Corresponding author

Correspondence to Mario Habek.

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Financial and competing interest disclosure

None of the authors have relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Funding

This study was funded by the Installation Research project HRZZ UIP-11-2013–2622 of the Croatian Science Foundation.

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Habek, M., Crnošija, L., Lovrić, M. et al. Sympathetic cardiovascular and sudomotor functions are frequently affected in early multiple sclerosis. Clin Auton Res 26, 385–393 (2016). https://doi.org/10.1007/s10286-016-0370-x

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  • DOI: https://doi.org/10.1007/s10286-016-0370-x

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