Parkinsonian traits in amyotrophic lateral sclerosis (ALS): a prospective population-based study
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.
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.
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.
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.
KeywordsAmyotrophic lateral sclerosis Parkinsonian Positron emission tomography Population-based study
Amyotrophic lateral sclerosis
Piemonte and Valle d’Aosta Register for ALS
ALS patients with co-morbid parkinsonian disorder
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.
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.
Compliance with ethical standards
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.
- 7.Pupillo E, Bianchi E, Messina P, Chiveri L, Lunetta C, Corbo M, Filosto M, Lorusso L, Marin B, Mandrioli J et al (2015) Extrapyramidal and cognitive signs in amyotrophic lateral sclerosis: a population based cross-sectional study. Amyotroph Lateral Scler Frontotemporal Degener 16(5–6):324–330CrossRefGoogle Scholar
- 12.Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R et al (2008) Movement disorder society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 23(15):2129–2170CrossRefGoogle Scholar
- 13.Strong MJ, Grace GM, Freedman M, Lomen-Hoerth C, Woolley S, Goldstein LH, Murphy J, Shoesmith C, Rosenfeld J, Leigh PN et al (2009) Consensus criteria for the diagnosis of frontotemporal cognitive and behavioural syndromes in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 10(3):131–146CrossRefGoogle Scholar
- 22.Boeve BF, Boylan KB, Graff-Radford NR, DeJesus-Hernandez M, Knopman DS, Pedraza O, Vemuri P, Jones D, Lowe V, Murray ME et al (2012) Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72. Brain 135(Pt 3):765–783CrossRefGoogle Scholar
- 31.Worker A, Blain C, Jarosz J, Chaudhuri KR, Barker GJ, Williams SC, Brown RG, Leigh PN, Dell’Acqua F, Simmons A (2014) Diffusion tensor imaging of Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy: a tract-based spatial statistics study. PLoS One 9(11):e112638CrossRefGoogle Scholar