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Heterogeneous pattern of autonomic dysfunction in Parkinson’s disease

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Abstract

Dysautonomic symptoms are frequent non-motor complaints in patients with Parkinson’s disease. Numerous neuropathological studies have shown that Lewy bodies and neurites, the pathological hallmarks of Parkinson’s disease, are widely distributed throughout the peripheral autonomic nervous systems and across end organs. However, few investigations integrally explored the symptoms and physiology of dysautonomia in Parkinson’s disease. We, therefore, performed a comprehensive evaluation of the autonomic function in a prospective group of 45 patients with idiopathic Parkinson’s disease. Autonomic components (pupillomotor, tear, salivary, cardiovascular, digestive, urinary, sexual, sudomotor functions and skin sensitivity) were evaluated using questionnaires and functional tests. Skin biopsy was performed for intraepidermal nerve fibre density quantification. In addition, all patients underwent polysomnography and a complete neuropsychological and neurological assessment. The analysis association of autonomic components showed that dysautonomic signs and symptoms were heterogeneously distributed among patients. Skin denervation as assessed by intraepidermal nerve fibre density quantification was only associated with quantitative thermal sensory testing (OR = 12.0, p = 0.02), constipation (OR = 5.5, p = 0.01) and ocular dryness symptoms (OR = 8.29, p = 0.04). Cognitive alteration was associated with cardiovascular symptoms (OR = 4.33, p = 0.03) and dysfunction (OR = 5.83, p = 0.02) as well as with constipation (OR = 5.38, p = 0.02). Axial motor impairment and rapid eye movement (REM) sleep behaviour disorder were not related to any of the autonomic complaint or dysfunction. Our results show that autonomic functions are affected in a heterogeneous pattern in Parkinson’s disease, thereby suggesting that the progression of autonomic dysfunction follows an erratic rather than a stepwise progression.

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Abbreviations

ANS:

Autonomic nervous system

ENS:

Enteric nervous system

IENF:

Intraepidermal nerve fibre

MDRS:

Mattis dementia rating scale

MMSE:

Mini-mental state examination

MoCA:

Montreal cognitive assessment

NCV:

Nerve conduction velocity

NMS-Quest:

Non-motor symptoms questionnaire

PD:

Parkinson’s disease

QST:

Quantitative thermal sensory testing

RBD:

Rapid eye movement sleep behaviour disorder

REM:

Rapid eye movement

SCOPA-Aut:

SCales for Outcomes in PArkinson’s disease-autonomic symptoms

SSR:

Sympathetic skin response

UPDRS-III:

Unified Parkinson’s disease rating scale part III

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Acknowledgements

Laurence Richard, Fanny Maquin, Monique Marguerite, Aurélie Grateau, Marion Rigot, Monica Roy, Aurélie Delhumeau and Alexandra Gosseaume for technical assistance, collecting and monitoring data. Tiphaine Rouaud, Violaine Talmant, Mirela Faighel and Marylène Jacq-Foucher for their help in selecting patients. David Laplaud and Paul Sauleau for their advices regarding data analysis. Patients and relatives for giving their time in participating in the study.

Funding

Nantes University Hospital was the study promoter. This work was supported by a Grant from Nantes University Hospital (Appel d’offre interne 2012, Grant number RC12_0264) and France Parkinson.

Author information

Authors and Affiliations

  1. Inserm, U1235, 44035, Nantes, France

    Laurène Leclair-Visonneau, Thomas Clairembault, Cécile Préterre, Arnaud Peyre, Michel Neunlist & Pascal Derkinderen

  2. University Nantes, 44093, Nantes, France

    Laurène Leclair-Visonneau, Thomas Clairembault, Cécile Préterre, Arnaud Peyre, Philippe Damier, Michel Neunlist, Yann Péréon & Pascal Derkinderen

  3. Inserm, CIC-04, 44093, Nantes, France

    Laurène Leclair-Visonneau, Séverine Le Dily, Cécile Préterre, Arnaud Peyre, Philippe Damier & Pascal Derkinderen

  4. Laboratoire d’Explorations Fonctionnelles, CHU Nantes, 44093, Nantes, France

    Laurène Leclair-Visonneau, Arnaud Peyre & Yann Péréon

  5. Department of Neurology, Centre de Référence “Neuropathies Périphériques Rares”, CHU Limoges, 87042, Limoges, France

    Laurent Magy

  6. Plateforme de Biométrie, Département Promotion DRCI, CHU Nantes, 44093, Nantes, France

    Christelle Volteau

  7. Institut des Maladies de l’Appareil Digestif, CHU Nantes, 44093, Nantes, France

    Thomas Clairembault & Michel Neunlist

  8. Department of Neurology, CHU Nantes, 44093, Nantes, France

    Cécile Préterre, Philippe Damier & Pascal Derkinderen

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  1. Laurène Leclair-Visonneau
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  2. Laurent Magy
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Correspondence to Laurène Leclair-Visonneau.

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Ethical standard statement

This study was carried out in accordance with the Declaration of Helsinki, conducted with the approval of the local Ethical Committee (Comité de protection des personnes Ouest VI, France).

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415_2018_8789_MOESM1_ESM.xlsx

Supplementary material 1 (XLSX 14 kb) Supplementary Table 1. Autonomic nervous system intra and inter-component association tests. Data on ‘light-headed for some time’ and ‘when standing up’ are combined for clarity reasons, as well as data on cold and heat intolerance. A separate analysis shows that light-headed for some time and orthostatic hypotension test were significantly associated (p = 0.02)

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Leclair-Visonneau, L., Magy, L., Volteau, C. et al. Heterogeneous pattern of autonomic dysfunction in Parkinson’s disease. J Neurol 265, 933–941 (2018). https://doi.org/10.1007/s00415-018-8789-8

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  • DOI: https://doi.org/10.1007/s00415-018-8789-8

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