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Parkinsonian traits in amyotrophic lateral sclerosis (ALS): a prospective population-based study

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Abstract

Background

Amyotrophic lateral sclerosis (ALS) is characterized by a spectrum of phenotypes, but only a few studies have addressed the presence of parkinsonian (PK) symptoms. The aim of our study was to investigate the occurrence of PK features in a prospective population-based cohort of ALS patients, determining their demographic, clinical, neuropsychological and genetic characteristics, and identifying their morphological and functional imaging correlates.

Methods

A consecutive series of ALS patients were enrolled and prospectively followed for 2 years. Patients were classified according to the presence (ALS-PK) or absence (ALS) of PK signs, and they underwent neuropsychological testing, genetic analysis for the main ALS and PD genes, brain MRI and 18F-FDG-PET. ALS-PK patients underwent 123I-ioflupane SPECT.

Results

Out of 114 eligible patients, 101 (64 men; mean age at onset 65.1 years) were recruited. Thirty-one patients (30.7%) were classified as ALS-PK. Compared to ALS patients, ALS-PK patients were more frequently male, but did not differ for any other clinical, demographic or neuropsychological factors. 123I-ioflupane SPECT was normal in all but two ALS-PK patients. At 18F-FDG-PET, ALS-PK patients showed a relative hypometabolism in left cerebellum and a relatively more preserved metabolism in right insula and frontal regions; MRI fractional anisotropy was reduced in the sagittal stratum and increased in the retrolenticular part of the internal capsule.

Conclusions

In our study, about 30% of ALS patients showed PK signs. Neuroimaging data indicate that PK signs are due to the involvement of brain circuitries other than classical nigrostriatal ones, strengthening the hypothesis of ALS as a complex multisystem disease.

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Abbreviations

ALS:

Amyotrophic lateral sclerosis

PD:

Parkinson’s disease

PARALS:

Piemonte and Valle d’Aosta Register for ALS

FTD:

Frontotemporal dementia

ALS-PK:

ALS patients with co-morbid parkinsonian disorder

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Acknowledgements

The Project has been supported by Italian Ministry of Health (Ricerca Finalizzata Giovani Ricercatori 2010; GR-2010-2320550, PI AndC); AndC thanks ‘Vialli e Mauro Foundation’; AntC thanks ‘Magnetto Foundation’. This study was supported by Ministero dell’Istruzione, dell’Università e della Ricerca—MIUR project “Dipartimenti di Eccellenza 2018–2022” to ‘Rita Levi Montalcini’ Department of Neuroscience.

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Author notes

  1. Andrea Calvo, Adriano Chiò, Marco Pagani, Leonardo Lopiano, and Mario G. Rizzone equally contributed to the paper.

Authors and Affiliations

  1. Department of Neuroscience “Rita Levi Montalcini”, ALS Center, University of Turin, Via Cherasco 15, 1026, Turin, Italy

    Andrea Calvo, Adriano Chiò, Stefania Cammarosano, Cristina Moglia, Luca Solero, Umberto Manera, Maura Brunetti, Marco Barberis, Rosario Vasta, Barbara Iazzolino & Antonio Canosa

  2. Department of Neuroscience “Rita Levi Montalcini”, Movement Disorders Center, University of Turin, Turin, Italy

    Tiziana Martone, Carlo Alberto Artusi, Elisa Montanaro, Alberto Romagnolo, Leonardo Lopiano & Mario G. Rizzone

  3. Institute of Cognitive Sciences and Technologies, CNR, Rome, Italy

    Marco Pagani

  4. Department of Nuclear Medicine, Karolinska Hospital Stockholm, Solna, Sweden

    Marco Pagani

  5. Division of Function and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 141 86, Stockholm, Sweden

    Tie-Qiang Li

  6. Division of MR Physics, Department of Medical Radiation and Nuclear Medicine, Karolinska University Hospital, 141 86, Stockholm, Sweden

    Tie-Qiang Li

  7. Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa and Polyclinic San Martino Hospital, Genoa, Italy

    Flavio Nobili

  8. Neurology Unit, Ospedali Riuniti di Rivoli, Rivoli, Italy

    Francesca Dematteis

  9. Nuclear Medicine Clinic, University of Turin, Turin, Italy

    Michele Balma & Giancarlo Castellano

  10. Positron Emission Tomography Centre IRMET S.p.A., Affidea, Turin, Italy

    Angelina Cistaro

  11. Neuroradiology Unit, AOU Città della Salute e della Scienza di Torino, Turin, Italy

    Giovanna Carrara & Consuelo Valentini

Authors
  1. Andrea Calvo
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  2. Adriano Chiò
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Contributions

AC, AC, LL and MGR contributed to the fund raising, literature search, figures, study design, data collection, data analysis, data interpretation, writing, and revision of the manuscript. AC, AC, SC, FD, UM, CM, AR, BI and EM contributed to the data collection, data analysis, and revision of the manuscript. LS, UM, CAA and AC contributed to writing, data analysis and revision of the manuscript. MP, QT and FN contributed to data analysis, data interpretation, and revision of the manuscript. TM, MB, GC, MB, AC, GC and CV contributed to data collection, data analysis, data interpretation, and revision of the manuscript.

Corresponding author

Correspondence to Andrea Calvo.

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Conflicts of interest

Andrea Calvo reports no disclosure. Adriano Chiò reports personal fees from Biogen Idec, Cytokinetics, Mitsubishi Tanabe, and Neuraltus, outside the submitted work. Marco Pagani reports no disclosure. Stefania Cammarosano reports no disclosure. Francesca Dematteis reports no disclosure. Cristina Moglia reports no disclosure. Luca Solero reports no disclosure. Umberto Manera reports no disclosure. Tiziana Martone reports no disclosure. Maura Brunetti reports no disclosure. Michele Balma reports no disclosure. Giancarlo Castellano reports no disclosure. Marco Barberis reports no disclosure. Angelina Cistaro reports no disclosure. Carlo Alberto Artusi reports no disclosure. Elisa Montanaro reports no disclosure. Alberto Romagnolo reports no disclosure. Barbara Iazzolino reports no disclosure. Antonio Canosa reports no disclosure. Giovanna Carrara reports no disclosure. Consuelo Valentini reports no disclosure. Tie-Qiang Li reports no disclosure. Flavio Nobili reports no disclosure. Leonardo Lopiano reports no disclosure. Mario G. Rizzone reports no disclosure.

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Calvo, A., Chiò, A., Pagani, M. et al. Parkinsonian traits in amyotrophic lateral sclerosis (ALS): a prospective population-based study. J Neurol 266, 1633–1642 (2019). https://doi.org/10.1007/s00415-019-09305-0

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