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Does fatigue in Parkinson’s disease correlate with autonomic nervous system dysfunction?

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Abstract

Background

Despite its negative impact on quality of life, fatigue in Parkinson’s disease (PD) remains an under-recognized issue and the underlying pathology is undetermined.

Objective

To contribute at understanding the pathogenesis of fatigue in a naturalistic cohort of cognitively intact PD patients.

Methods

In a Caucasian population of PD patients (n = 27), we evaluated to what extent fatigue (quantified as PFS-16 score) is associated with PD duration and with autonomic dysfunction, studied by both MIBG scintigraphy and autonomic nervous system testing. The latter included the head-up tilt test, Valsalva maneuver, deep breathing, and handgrip tests.

Results

PFS-16 score correlated with disease duration (R = 0.57, p = 0.002). Fatigue showed a clear correlation with deep breathing test (R = − 0.53, p = 0.004) but not with the MIBG H/M ratios.

Conclusions

Our data are consistent with a multifactorial pathogenesis of fatigue and with effects of dopamine depletion in PD-related fatigue; on the other hand, our findings do not support a role for sympathetic denervation in PD-related fatigue.

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References

  1. Friedman JH, Friedman H (1993) Fatigue in Parkinson’s disease. Neurology 43:2016–2018

    Article  CAS  PubMed  Google Scholar 

  2. Karlsen K, Larsen JP, Tandberg E, Jørgensen K (1999) Fatigue in patients with Parkinson’s disease. Mov Disord 14:237–241

    Article  CAS  PubMed  Google Scholar 

  3. Herlofson K, Larsen JP (2003) The influence of fatigue on health-related quality of life in patients with Parkinsons disease. Acta Neurol Scand 107:1–6

    Article  CAS  PubMed  Google Scholar 

  4. Alves G, Wentzel-Larsen T, Larsen JP (2004) Is fatigue an independent and persistent symptom in patients with Parkinson disease? Neurology 63:1908–1911

    Article  CAS  PubMed  Google Scholar 

  5. Schifitto G, Friedman JH, Oakes D, Shulman L, Comella CL, Marek K, Fahn S, The Parkinson Study Group ELLDOPA Investigators (2008) Fatigue in levodopa-naive subjects with Parkinson disease. Neurology 71:481–485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Stocchi F, Abbruzzese G, Ceravolo R, Cortelli P, D'Amelio M, de Pandis MF, Fabbrini G, Pacchetti C, Pezzoli G, Tessitore A, Canesi M, Iannacone C, Zappia M, For the FORTE Study Group (2014) Prevalence of fatigue in Parkinson disease and its clinical correlates. Neurology 83:215–220

    Article  PubMed  Google Scholar 

  7. Lou JS, Kearns G, Oken B, Sexton G, Nutt J (2001) Exacerbated physical fatigue and mental fatigue in Parkinson’s disease. Mov Disord 16:190–196

    Article  CAS  PubMed  Google Scholar 

  8. Van Hilten JJ, Hoogland G, van der Velde EA, Middelkoop HA, Kerkhof GA, Roos RA (1993) Diurnal effects of motor activity and fatigue in Parkinson’s disease. J Neurol Neurosurg 56:874–877

    Article  Google Scholar 

  9. Chou KL, Persad CC, Patil PG (2012) Change in fatigue after bilateral subthalamic nucleus deep brain stimulation for Parkinson’s disease. Parkinsonism Relat Disord 18:510–513

    Article  PubMed  Google Scholar 

  10. Berardelli A, Conte A, Fabbrini G, Bologna M, Latorre A, Rocchi L, Suppa A (2012) Pathophysiology of pain and fatigue in Parkinson’s disease. Parkinsonism Relat Disord 18:S226–S228

    Article  PubMed  Google Scholar 

  11. Chou KL, Kotagal V, Bohnen NI (2016) Neuroimaging and clinical predictors of fatigue in Parkinson disease. Parkinsonism Relat Disord 23:45–49

    Article  PubMed  Google Scholar 

  12. Lou JS, Kearns G, Benice T, Oken B, Sexton G, Nutt J (2003) Levodopa improves physical fatigue in Parkinson's disease: a double-blind, placebo-controlled, crossover study. Mov Disord 18:1108–1114

    Article  PubMed  Google Scholar 

  13. Chaudhuri KR, Martinez-martin P, Antonini A et al (2013) Rotigotine and specific non-motor symptoms of Parkinson’s disease: post hoc analysis of RECOVER. Parkinsonism Relat Disord 19:660–665

    Article  Google Scholar 

  14. Stocchi F, investigators ADAGIO (2014) Benefits of treatment with rasagiline for fatigue symptoms in patients with early Parkinson's disease. Eur J Neurol 21:357–360

    Article  CAS  PubMed  Google Scholar 

  15. Pavese N, Metta V, Bose SK, Chaudhuri KR, Brooks DJ (2010) Fatigue in Parkinson’s disease is linked to striatal and limbic serotonergic dysfunction. Brain 133:3434–3443

    Article  PubMed  Google Scholar 

  16. Nakamura T, Hirayama M, Hara T, Hama T, Watanabe H, Sobue G (2011) Does cardiovascular autonomic dysfunction contribute to fatigue in Parkinson’s disease? Mov Disord 26:1869–1874

    Article  PubMed  Google Scholar 

  17. Friedman JH, Alves G, Hagell P, Marinus J, Marsh L, Martinez-Martin P, Goetz CG, Poewe W, Rascol O, Sampaio C, Stebbins G, Schrag A (2010) Fatigue rating scales critique and recommendations by the movement disorders society task force on rating scales for Parkinson’s disease. Mov Disord 25:805–822

    Article  PubMed  Google Scholar 

  18. Brown RG, Dittner A, Findley L, Wessely SC (2005) The Parkinson fatigue scale. Parkinsonism Relat Disord 11:49–55

    Article  CAS  PubMed  Google Scholar 

  19. Rocchi C, Pierantozzi M, Pisani V, Marfia GA, di Giorgio A, Stanzione P, Bernardi G, Stefani A (2012) The impact of rotigotine on cardiovascular autonomic function in early Parkinson's disease. Eur Neurol 68:187–192

    Article  CAS  PubMed  Google Scholar 

  20. Rocchi C, Pierantozzi M, Galati S, Chiaravalloti A, Pisani V, Prosperetti C, Lauretti B, Stampanoni Bassi M, Olivola E, Schillaci O, Stefani A (2015) Autonomic function tests and MIBG in Parkinson's disease: correlation to disease duration and motor symptoms. CNS Neurosci Ther 21:727–732

    Article  CAS  PubMed  Google Scholar 

  21. Chiaravalloti A, Stefani A, Tavolozza M et al (2012) Different patterns of cardiac sympathetic denervation in tremor-type compared to akinetic-rigid-type Parkinson's disease: molecular imaging with 123I-MIBG. Mol Med Rep 6:1337–1342

    Article  CAS  PubMed  Google Scholar 

  22. Tanaka M, Mizuno K, Yamaguti K et al (2011) Autonomic nervous alterations associated with daily level of fatigue. Behav Brain Funct 27:7–46

    Google Scholar 

  23. Chalencon S, Busso T, Lacour JR, Garet M, Pichot V, Connes P, Gabel CP, Roche F, Barthélémy JC (2012) A model for the training effects in swimming demonstrates a strong relationship between parasympathetic activity, performance and index of fatigue. PLoS One 7:e52636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Morita A, Okuma Y, Kamei S, Yoshii F, Yamamoto T, Hashimoto S, Utsumi H, Hatano T, Hattori N, Matsumura M, Takahashi K, Nogawa S, Watanabe Y, Miyamoto T, Miyamoto M, Hirata K (2011) Pramipexole reduces the prevalence of fatigue in patients with Parkinson’s disease. Intern Med 50:2163–2168

    Article  CAS  PubMed  Google Scholar 

  25. Chaudhuri A, Behan PO (2004) Fatigue in neurological disorders. Lancet 363:978–988

    Article  PubMed  Google Scholar 

  26. Ossig C, Sippel D, Fauser M, Gandor F, Jost WH, Ebersbach G, Storch A (2017) Timing and kinetics of nonmotor fluctuations in advanced Parkinson's disease. J Parkinsons Dis 7:325–330

    Article  PubMed  Google Scholar 

  27. Tessitore A, Giordano A, De Micco R et al (2016) Functional connectivity underpinnings of fatigue in "drug-naïve" patients with Parkinson's disease. Mov Disord 31:1497–1505

    Article  PubMed  Google Scholar 

  28. Olivola E, Pierantozzi M, Imbriani P et al (2014) Serotonin impairment in CSF of PD patients, without an apparent clinical counterpart. PLoS One 9:e1

    Article  CAS  Google Scholar 

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Author notes

  1. Enrica Olivola and Livia Brusa contributed equally to this work.

Authors and Affiliations

  1. UOSD Parkinson’s Center, Department of Systems Medicine, University of Rome “Tor Vergata”, Viale Oxford, 81, 00133, Rome, Italy

    Enrica Olivola, Camilla Rocchi, Claudio Liguori, Rocco Cerroni, Mariangela Pierantozzi & Alessandro Stefani

  2. IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Italy

    Enrica Olivola, Orazio Schillaci & Agostino Chiaravalloti

  3. Ospedale S. Eugenio, ASL RMC, Rome, Italy

    Livia Brusa

  4. Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy

    Orazio Schillaci & Agostino Chiaravalloti

  5. Department of Neurology, Institute for Research and Medical Care, IRCCS San Raffaele, Rome, Italy

    Fabrizio Stocchi

Authors
  1. Enrica Olivola
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  2. Livia Brusa
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  3. Camilla Rocchi
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  4. Orazio Schillaci
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  5. Claudio Liguori
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  6. Rocco Cerroni
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  7. Mariangela Pierantozzi
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  8. Agostino Chiaravalloti
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  9. Alessandro Stefani
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  10. Fabrizio Stocchi
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Corresponding author

Correspondence to Alessandro Stefani.

Ethics declarations

The study was approved by local ethics committee and informed consent was provided by all subjects.

Conflict of interest

The authors declare that they have no conflict of interest.

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Olivola, E., Brusa, L., Rocchi, C. et al. Does fatigue in Parkinson’s disease correlate with autonomic nervous system dysfunction?. Neurol Sci 39, 2169–2174 (2018). https://doi.org/10.1007/s10072-018-3569-x

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  • DOI: https://doi.org/10.1007/s10072-018-3569-x

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