Advertisement

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

  • Andrea CalvoEmail author
  • Adriano Chiò
  • Marco Pagani
  • Stefania Cammarosano
  • Francesca Dematteis
  • Cristina Moglia
  • Luca Solero
  • Umberto Manera
  • Tiziana Martone
  • Maura Brunetti
  • Michele Balma
  • Giancarlo Castellano
  • Marco Barberis
  • Angelina Cistaro
  • Carlo Alberto Artusi
  • Rosario Vasta
  • Elisa Montanaro
  • Alberto Romagnolo
  • Barbara Iazzolino
  • Antonio Canosa
  • Giovanna Carrara
  • Consuelo Valentini
  • Tie-Qiang Li
  • Flavio Nobili
  • Leonardo Lopiano
  • Mario G. Rizzone
Original Communication

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.

Keywords

Amyotrophic lateral sclerosis Parkinsonian Positron emission tomography Population-based study 

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

Notes

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.

Author 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.

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.

Supplementary material

415_2019_9305_MOESM1_ESM.docx (26 kb)
Supplementary material 1 (DOCX 25 kb)
415_2019_9305_MOESM2_ESM.docx (33 kb)
Supplementary material 2 (DOCX 33 kb)

References

  1. 1.
    van Es MA, Hardiman O, Chio A, Al-Chalabi A, Pasterkamp RJ, Veldink JH, van den Berg LH (2017) Amyotrophic lateral sclerosis. Lancet 390(10107):2084–2098CrossRefGoogle Scholar
  2. 2.
    Phukan J, Elamin M, Bede P, Jordan N, Gallagher L, Byrne S, Lynch C, Pender N, Hardiman O (2012) The syndrome of cognitive impairment in amyotrophic lateral sclerosis: a population-based study. J Neurol Neurosurg Psychiatry 83(1):102–108CrossRefGoogle Scholar
  3. 3.
    Montuschi A, Iazzolino B, Calvo A, Moglia C, Lopiano L, Restagno G, Brunetti M, Ossola I, Lo Presti A, Cammarosano S et al (2015) Cognitive correlates in amyotrophic lateral sclerosis: a population-based study in Italy. J Neurol Neurosurg Psychiatry 86(2):168–173CrossRefGoogle Scholar
  4. 4.
    Al-Chalabi A, Hardiman O, Kiernan MC, Chio A, Rix-Brooks B, van den Berg LH (2016) Amyotrophic lateral sclerosis: moving towards a new classification system. Lancet Neurol 15(11):1182–1194CrossRefGoogle Scholar
  5. 5.
    Brait K, Fahn S, Schwarz GA (1973) Sporadic and familial parkinsonism and motor neuron disease. Neurology 23(9):990–1002CrossRefGoogle Scholar
  6. 6.
    Pradat PF, Bruneteau G, Munerati E, Salachas F, Le Forestier N, Lacomblez L, Lenglet T, Meininger V (2009) Extrapyramidal stiffness in patients with amyotrophic lateral sclerosis. Mov Disord 24(14):2143–2148CrossRefGoogle Scholar
  7. 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
  8. 8.
    Brooks BR, Miller RG, Swash M, Munsat TL (2000) World federation of neurology research group on motor neuron D: El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1(5):293–299CrossRefGoogle Scholar
  9. 9.
    Chio A, Calvo A, Moglia C, Mazzini L, Mora G (2011) group Ps: phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study. J Neurol Neurosurg Psychiatry 82(7):740–746CrossRefGoogle Scholar
  10. 10.
    Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE et al (2015) MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 30(12):1591–1601CrossRefGoogle Scholar
  11. 11.
    Ling H, Kara E, Bandopadhyay R, Hardy J, Holton J, Xiromerisiou G, Lees A, Houlden H, Revesz T (2013) TDP-43 pathology in a patient carrying G2019S LRRK2 mutation and a novel p.Q124E MAPT. Neurobiol Aging 34(12):2889 (e2885–2889) CrossRefGoogle Scholar
  12. 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. 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
  14. 14.
    Armstrong MJ, Litvan I, Lang AE, Bak TH, Bhatia KP, Borroni B, Boxer AL, Dickson DW, Grossman M, Hallett M et al (2013) Criteria for the diagnosis of corticobasal degeneration. Neurology 80(5):496–503CrossRefGoogle Scholar
  15. 15.
    Pinkhardt EH, Sperfeld AD, Gdynia HJ, Ludolph AC, Kassubek J (2009) The combination of dopa-responsive parkinsonian syndrome and motor neuron disease. Neurodegener Dis 6(3):95–101CrossRefGoogle Scholar
  16. 16.
    Williams TL, Shaw PJ, Lowe J, Bates D, Ince PG (1995) Parkinsonism in motor neuron disease: case report and literature review. Acta Neuropathol 89(3):275–283CrossRefGoogle Scholar
  17. 17.
    Desai J, Swash M (1999) Extrapyramidal involvement in amyotrophic lateral sclerosis: backward falls and retropulsion. J Neurol Neurosurg Psychiatry 67(2):214–216CrossRefGoogle Scholar
  18. 18.
    Zoccolella S, Palagano G, Fraddosio A, Russo I, Ferrannini E, Serlenga L, Maggio F, Lamberti S, Iliceto G (2002) ALS-plus: 5 cases of concomitant amyotrophic lateral sclerosis and parkinsonism. Neurol Sci 23(Suppl 2):S123–S124CrossRefGoogle Scholar
  19. 19.
    Manno C, Lipari A, Bono V, Taiello AC, La Bella V (2013) Sporadic Parkinson disease and amyotrophic lateral sclerosis complex (Brait-Fahn-Schwartz disease). J Neurol Sci 326(1–2):104–106CrossRefGoogle Scholar
  20. 20.
    Belin J, Gordon PH, Guennoc AM, De Toffol B, Corcia P (2015) Brait-Fahn-Schwarz disease: the missing link between ALS and Parkinson’s disease. Amyotroph Lateral Scler Frontotemporal Degener 16(1–2):135–136CrossRefGoogle Scholar
  21. 21.
    Gilbert RM, Fahn S, Mitsumoto H, Rowland LP (2010) Parkinsonism and motor neuron diseases: twenty-seven patients with diverse overlap syndromes. Mov Disord 25(12):1868–1875CrossRefGoogle Scholar
  22. 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
  23. 23.
    Theuns J, Verstraeten A, Sleegers K, Wauters E, Gijselinck I, Smolders S, Crosiers D, Corsmit E, Elinck E, Sharma M et al (2014) Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease. Neurology 83(21):1906–1913CrossRefGoogle Scholar
  24. 24.
    Borasio GD, Linke R, Schwarz J, Schlamp V, Abel A, Mozley PD, Tatsch K (1998) Dopaminergic deficit in amyotrophic lateral sclerosis assessed with [I-123] IPT single photon emission computed tomography. J Neurol Neurosurg Psychiatry 65(2):263–265CrossRefGoogle Scholar
  25. 25.
    Takahashi H, Snow BJ, Bhatt MH, Peppard R, Eisen A, Calne DB (1993) Evidence for a dopaminergic deficit in sporadic amyotrophic lateral sclerosis on positron emission scanning. Lancet 342(8878):1016–1018CrossRefGoogle Scholar
  26. 26.
    Hideyama T, Momose T, Shimizu J, Tsuji S, Kwak S (2006) A positron emission tomography study on the role of nigral lesions in parkinsonism in patients with amyotrophic lateral sclerosis. Arch Neurol 63(12):1719–1722CrossRefGoogle Scholar
  27. 27.
    Teune LK, Renken RJ, de Jong BM, Willemsen AT, van Osch MJ, Roerdink JB, Dierckx RA, Leenders KL (2014) Parkinson’s disease-related perfusion and glucose metabolic brain patterns identified with PCASL-MRI and FDG-PET imaging. NeuroImage Clinical 5:240–244CrossRefGoogle Scholar
  28. 28.
    Holtbernd F, Ma Y, Peng S, Schwartz F, Timmermann L, Kracht L, Fink GR, Tang CC, Eidelberg D, Eggers C (2015) Dopaminergic correlates of metabolic network activity in Parkinson’s disease. Hum Brain Mapp 36(9):3575–3585CrossRefGoogle Scholar
  29. 29.
    Teune LK, Bartels AL, de Jong BM, Willemsen AT, Eshuis SA, de Vries JJ, van Oostrom JC, Leenders KL (2010) Typical cerebral metabolic patterns in neurodegenerative brain diseases. Mov Disord 25(14):2395–2404CrossRefGoogle Scholar
  30. 30.
    Zheng Z, Shemmassian S, Wijekoon C, Kim W, Bookheimer SY, Pouratian N (2014) DTI correlates of distinct cognitive impairments in Parkinson’s disease. Hum Brain Mapp 35(4):1325–1333CrossRefGoogle Scholar
  31. 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
  32. 32.
    Kraus MF, Susmaras T, Caughlin BP, Walker CJ, Sweeney JA, Little DM (2007) White matter integrity and cognition in chronic traumatic brain injury: a diffusion tensor imaging study. Brain 130(Pt 10):2508–2519CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Andrea Calvo
    • 1
    Email author
  • Adriano Chiò
    • 1
  • Marco Pagani
    • 3
    • 4
  • Stefania Cammarosano
    • 1
  • Francesca Dematteis
    • 8
  • Cristina Moglia
    • 1
  • Luca Solero
    • 1
  • Umberto Manera
    • 1
  • Tiziana Martone
    • 2
  • Maura Brunetti
    • 1
  • Michele Balma
    • 9
  • Giancarlo Castellano
    • 9
  • Marco Barberis
    • 1
  • Angelina Cistaro
    • 10
  • Carlo Alberto Artusi
    • 2
  • Rosario Vasta
    • 1
  • Elisa Montanaro
    • 2
  • Alberto Romagnolo
    • 2
  • Barbara Iazzolino
    • 1
  • Antonio Canosa
    • 1
  • Giovanna Carrara
    • 11
  • Consuelo Valentini
    • 11
  • Tie-Qiang Li
    • 5
    • 6
  • Flavio Nobili
    • 7
  • Leonardo Lopiano
    • 2
  • Mario G. Rizzone
    • 2
  1. 1.Department of Neuroscience “Rita Levi Montalcini”, ALS CenterUniversity of TurinTurinItaly
  2. 2.Department of Neuroscience “Rita Levi Montalcini”, Movement Disorders CenterUniversity of TurinTurinItaly
  3. 3.Institute of Cognitive Sciences and Technologies, CNRRomeItaly
  4. 4.Department of Nuclear MedicineKarolinska Hospital StockholmSolnaSweden
  5. 5.Division of Function and Technology, Department of Clinical Science, Intervention and TechnologyKarolinska InstitutetStockholmSweden
  6. 6.Division of MR Physics, Department of Medical Radiation and Nuclear MedicineKarolinska University HospitalStockholmSweden
  7. 7.Clinical Neurology, Department of Neuroscience (DINOGMI)University of Genoa and Polyclinic San Martino HospitalGenoaItaly
  8. 8.Neurology UnitOspedali Riuniti di RivoliRivoliItaly
  9. 9.Nuclear Medicine ClinicUniversity of TurinTurinItaly
  10. 10.Positron Emission Tomography Centre IRMET S.p.A., AffideaTurinItaly
  11. 11.Neuroradiology UnitAOU Città della Salute e della Scienza di TorinoTurinItaly

Personalised recommendations