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Beyond 35 years of Parkinson’s disease: a comprehensive clinical and instrumental assessment

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Abstract

Background

We sought to characterize the clinical, neuropsychological, electrophysiological, and neuroimaging features of Parkinson’s disease (PD) after over 35 years since the onset of motor symptoms.

Methods

Five consecutively consenting PD patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) were recruited in a cross-sectional study of motor (Unified PD Rating Scale section-III), non-motor (Non-Motor Symptoms Scale), autonomic (Scale for Outcome in PD-Autonomic), and neuropsychological features associated with the very advanced phase of PD. In addition, patients underwent neurophysiological (autonomic tests and nerve conduction studies) and neuroimaging (brain MRI, 123I-FP-CIT SPECT, and 123I-MIBG myocardial scintigraphy) studies, as well as a genetic analysis of 34 genes and single nucleotide polymorphisms associated with PD.

Results

There was a sustained motor response to l-dopa (range 14.4–35.6%), STN-DBS (23.3–38.4%), and l-dopa plus STN-DBS (37.8–63.0%). There were mild-to-moderate non-motor symptoms (range 19–83 on a scale of 0 to 360) and autonomic dysfunction (8–28 on a scale of 0–69). Two patients were demented, one had mild cognitive impairment, and two were cognitively preserved. Three patients had a sensory-axonal peripheral neuropathy and two a moderate-to-severe autonomic neuropathy. All cases showed a complete nigro-striatal dopaminergic denervation and a severe cardiovascular noradrenergic denervation. The brain MRI revealed only moderate frontal atrophy. The genetic tests were unremarkable.

Conclusions

Even after more than 35 years of disease, L-dopa  and STN-DBS remain effective on PD cardinal symptoms. Although axial, autonomic, and neuropsychological features may become key determinants of disability, some patients maintain a satisfactory quality of life, without significant motor and non-motor impairment.

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Funding

Nothing to declare.

Author information

Author notes

  1. Alberto Romagnolo and Margherita Fabbri contributed equally to this manuscript.

Authors and Affiliations

  1. Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Via Cherasco 15, 10124, Turin, Italy

    Alberto Romagnolo, Margherita Fabbri, Elisa Montanaro, Tiziana Martone, Stefano Goldwurm, Mario Giorgio Rizzone & Leonardo Lopiano

  2. Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisbon, Portugal

    Margherita Fabbri

  3. Department of Neurology, Gardner Family Center for Parkinson’s Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA

    Aristide Merola

  4. Department of Psychology, University of Turin, Via Verdi 10, 10124, Turin, Italy

    Sara Palermo

  5. Medical Genetics Laboratory, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Agostino Seresini

  6. Parkinson Institute, ASST “G.Pini-CTO”, Via Bignami 1, Milan, 20133, Italy

    Stefano Goldwurm

Authors
  1. Alberto Romagnolo
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  2. Margherita Fabbri
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Contributions

AR: conception and design of the study; acquisition, analysis and interpretation of data; writing of the first draft and review and critique of the manuscript. MF: design of the study; acquisition, analysis and interpretation of data; writing of the first draft and review and critique of the manuscript. AM: design of the study; acquisition, analysis and interpretation of data; review and critique of the manuscript. EM: design of the study; acquisition, analysis and interpretation of data; review and critique of the manuscript. SP: design of the study; acquisition, analysis and interpretation of data; review and critique of the manuscript. TM: design of the study; analysis and interpretation of data; review and critique of the manuscript. AS: design of the study; analysis and interpretation of data; review and critique of the manuscript. SG: design of the study; analysis and interpretation of data; review and critique of the manuscript. MGR: conception and design of the study; analysis and interpretation of data; review and critique of the manuscript. LL: conception and design of the study; analysis and interpretation of data; review and critique of the manuscript. All the co-authors listed above gave their final approval of this manuscript version.

Corresponding author

Correspondence to Alberto Romagnolo.

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Conflicts of interest

Dr. Romagnolo has received grant support and speaker honoraria from AbbVie, speaker honoraria from Chiesi Farmaceutici and travel grants from Lusofarmaco and UCB Pharma. Dr. Fabbri reports no disclosures. Dr. Merola is supported by NIH (KL2 TR001426) and has received speaker honoraria from CSL Behring, Abbvie, and Cynapsus Therapeutics. He has received grant support from Lundbeck. Dr. Montanaro reports no disclosures. Dr. Palermo reports no disclosures. Dr. Martone reports no disclosures. Dr. Seresini reports no disclosures. Dr. Goldwurm reports no disclosures. Dr. Rizzone has received honoraria for lecturing and travel grants from Medtronic and Zambon. Dr. Lopiano has received honoraria for lecturing and travel grants from Medtronic, UCB Pharma and AbbVie.

Ethical standard

The authors declare that they acted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. The local institutional review board (Comitato Etico Interaziendale Città della Salute e della Scienza di Torino; CS/855; protocol number 475) approved the study and all participants provided written informed consent. The demented patients gave their informed assent, and a written informed consent was obtained from their legal representative.

Data access and responsibility statement

A. Romagnolo had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Romagnolo, A., Fabbri, M., Merola, A. et al. Beyond 35 years of Parkinson’s disease: a comprehensive clinical and instrumental assessment. J Neurol 265, 1989–1997 (2018). https://doi.org/10.1007/s00415-018-8955-z

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  • DOI: https://doi.org/10.1007/s00415-018-8955-z

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